Sunflower Health Plan Concert Genetic Testing: Prenatal and Preconception Carrier Screening (PDF) Form

Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 CONCERT GENETIC TESTING: PRENATAL AND PRECONCEPTION CARRIER SCREENING See Important Reminder at the end of this policy for important regulatory and legal information. OVERVIEW There are more than 1,300 inherited recessive disorders (autosomal or X-linked) that affect 30 out of every 10,000 children. Some diseases have limited impact on either length or quality of life, while others are uniformly fatal in infancy or childhood. By definition, autosomal recessive disorders arise when both parents pass on disease-causing copies of genes to a child. X-linked recessive conditions arise when a disease-causing version of a gene is on the X-chromosome and is passed to a male child who only has one copy of the X-chromosome. Carrier screening is performed to identify individuals at risk of having offspring with inherited recessive or X-linked single-gene disorders. Carriers are typically asymptomatic but can pass disease-causing variants to their offspring. Carrier screening may be performed in the prenatal or preconception periods. Risk-based carrier screening is performed in individuals who have an increased risk to be a carrier based on population carrier frequency, ethnicity, and/or family history. Expanded carrier screening (ECS) involves screening individuals or couples for disorders in many genes simultaneously (up to 100s) by next-generation sequencing. ECS panels may screen for diseases that are present with increased frequency in specific populations, but also include a wide range of diseases for which the individual seeking testing is not at increased risk for positive carrier status. The conditions included on ECS panels are not standardized and the panels may include conditions that are not well understood and for which there are no existing professional guidelines. POLICY REFERENCE TABLE Below are a list of higher volume tests and the associated laboratories for each coverage criteria section. This list is not all inclusive. 1 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 Coding Implications This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. Common Common CPT Codes CPT Codes Common ICD Common ICD Codes Codes Ref Ref 81243, 81257, 81243, 81257, 81329, 81443 81329, 81443 O09, Z13, O09, Z13, Z31, Z34, Z31, Z34, Z36, Z84 Z36, Z84 4, 6, 7 4, 6, 7 Coverage Criteria Coverage Criteria Sections Sections Expanded Carrier Expanded Carrier Screening Panels Screening Panels Example Tests (Labs) Example Tests (Labs) Foresight Carrier Screen (Myriad) Foresight Carrier Screen (Myriad) Inheritest 500 Plus Panel (LabCorp) Inheritest 500 Plus Panel (LabCorp) GeneSeq Plus (LabCorp) GeneSeq Plus (LabCorp) Comprehensive Carrier Screening Comprehensive Carrier Screening (Invitae) (Invitae) Comprehensive Carrier Screen without Comprehensive Carrier Screen without X-linked Disorders (Invitae) X-linked Disorders (Invitae) Broad Carrier Screen (Invitae) Broad Carrier Screen (Invitae) Broad Carrier Screen without X-linked Broad Carrier Screen without X-linked Disorders (Invitae) Disorders (Invitae) Inheritest Comprehensive Panel Inheritest Comprehensive Panel (Labcorp) (Labcorp) QHerit™ Expanded Carrier Screen QHerit™ Expanded Carrier Screen (Quest Diagnostics) (Quest Diagnostics) Horizon 14 (Natera) Horizon 14 (Natera) Horizon 27 (Natera) Horizon 27 (Natera) Horizon 274 (Natera) Horizon 274 (Natera) Basic Carrier Screening Basic Carrier Screening Panels (Cystic Fibrosis, Panels (Cystic Fibrosis, Spinal Muscular Atrophy, Spinal Muscular Atrophy, Fragile X, Fragile X, Hemoglobinopathies, not Hemoglobinopathies, not more than 14 genes) more than 14 genes) Inheritest Core Panel (LabCorp) Inheritest Core Panel (LabCorp) Inheritest Carrier Screen, Society- Inheritest Carrier Screen, Society- guided Panel (14 Genes) (LabCorp) guided Panel (14 Genes) (LabCorp) Prenatal Carrier Panel (Quest Prenatal Carrier Panel (Quest Diagnostics) Diagnostics) Foresight Fundamental Panel (Myriad) Foresight Fundamental Panel (Myriad) Core Carrier Screen (Invitae) Core Carrier Screen (Invitae) Cystic Fibrosis Carrier Screening Cystic Fibrosis Carrier Screening 81220, 81329, 81220, 81329, 81243, 81257 81243, 81257 O09, Z13, O09, Z13, Z31, Z34, Z31, Z34, Z36, Z84 Z36, Z84 4, 5 4, 5 2 O09, Z13, Z31, Z36, Z83.49 1, 2, 5, 13 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 CFTR Known Familial Variant Analysis Targeted Variants: CFTR (PreventionGenetics) CFTR Sequencing and/or Deletion/Duplication Analysis, or Mutation Panel Cystic Fibrosis Complete Rare Variant Analysis, Entire Gene Sequence (Quest Diagnostics) Cystic Fibrosis Gene Deletion or Duplication (Quest Diagnostics) Cystic Fibrosis (CF) Profile, 32 mutations, DNA Analysis (LabCorp) Cystic Fibrosis Screen (Quest Diagnostics) 81221 81223 81222 81220 CFTR Intron 9 PolyT and TG Analysis (previously called Intron 8 polyT/TG Analysis) CFTR Intron 8 Poly-T Analysis (Quest Diagnostics) 81224 Spinal Muscular Atrophy Carrier Screening SMN1 Targeted Variant Analysis Known Variant Testing-SMN1 (Nemours) SMN1 Targeted Variant - 2 Variants Test (GeneDx) 81337, 81403 O09, Z13, Z31, Z34, Z36, Z84 5, 9 SMN1 Sequencing and/or Deletion/Duplication and SMN2 Deletion/Duplication Analysis Spinal Muscular Atrophy Carrier Test (Natera) 81329, 81336, 81401, 81405 Fragile X Syndrome Carrier Screening FMR1 Repeat Analysis Fragile X Syndrome, PCR with Reflex to Southern Blot (LabCorp) Fragile X Syndrome, PCR and Southern Blot Analysis (LabCorp) 81243, 81244 O09, Z13, Z31, Z34, Z36, Z84 5, 12 Hemoglobinopathy Carrier Screening HBA1, HBA2, or HBB Targeted Variant Analysis Alpha-Globin Common Mutation Analysis (Quest Diagnostics) HBA1 Targeted Variant-Single Test (GeneDx) HBA2 Targeted Variant-Single Test (GeneDx) 81257, 81258 O09, Z13, Z31, Z34, Z36, Z84 5 Targeted Variant-HBB 81361, 81362 3 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 HBA1, HBA2, or HBB Sequencing and/or Deletion/Duplication Analysis (PreventionGenetics) Alpha-Globin Gene Sequencing (Quest Diagnostics) 81259, 81269, 81363, 81364 HBA1 Deletion/Duplication (GeneDx) HBA2 Deletion/Duplication (GeneDx) HBB Carrier-Full Gene Sequencing and Deletion/Duplication (Invitae) Ashkenazi Jewish Carrier Panel Testing Ashkenazi Jewish Carrier Panel Testing Ashkenazi Jewish Panel (Quest Diagnostics) 81412 5, 8 O09, Z13, Z31, Z34, Z36, Z84 Duchenne and Becker Muscular Dystrophy Carrier Screening DMD Targeted Variant Analysis Targeted Variants-DMD (PreventionGenetics) DMD Sequencing and/or Deletion/Duplication Analysis Duchenne/Becker MD (DMD) Gene Sequencing (GeneDx) Duchenne/Becker MD (DMD) Del/Dup (GeneDx) 81408, 81403 O09, Z13, Z31, Z34, Z36, Z84 81161, 81408 10, 11 Genomic Unity DMD Gene Analysis (Variantyx) 0218U General Criteria for Targeted Carrier Screening General Criteria for Targeted Carrier Screening Varies Z14, Z15, Z31 3, 4, 5 81174, 81190, 81200, 81205, 81209, 81242, 81247, 81248, 81250, 81251, 81253, 81254, 81289, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408 4 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 OTHER RELATED POLICIES This policy document provides coverage criteria for Prenatal and Preconception Carrier Screening. Please refer to: ● ● ● ● ● ● ● ● Genetic Testing: Prenatal Diagnosis (via amniocentesis, CVS, or PUBS) and Pregnancy Loss for coverage related to prenatal and pregnancy loss diagnostic genetic testing intended to diagnose genetic conditions following amniocentesis, chorionic villus sampling, or pregnancy loss. Genetic Testing: Noninvasive Prenatal Screening (NIPS) for coverage criteria related to prenatal cell-free DNA screening tests. Genetic Testing: Preimplantation Genetic Testing for coverage criteria related to genetic testing of embryos prior to in vitro fertilization. Genetic Testing: Multisystem Inherited Disorders, Intellectual Disability and Developmental Delay for coverage criteria related to suspected multisystem genetic conditions in the postnatal period. Genetic Testing: Hearing Loss for coverage related to diagnostic genetic testing for hereditary hearing loss. Genetic Testing: Hematologic Conditions (non-cancerous) for coverage related to diagnostic genetic testing for alpha-thalassemia and other hemoglobinopathies. Genetic Testing: Metabolic, Endocrine, and Mitochondrial Disorders for coverage related to diagnostic genetic testing for mitochondrial and other disorders. Genetic Testing: General Approach to Genetic Testing for coverage criteria related to carrier screening that is not specifically discussed in this or other non-general policies. CRITERIA It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria: 5 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 EXPANDED CARRIER SCREENING PANELS I. Expanded carrier screening panels (81243, 81257, 81329, 81443*) may be considered medically necessary when: A. The member/enrollee is considering pregnancy or is currently pregnant, AND B. The panel includes the genes CFTR and SMN1. II. Expanded carrier screening panels (81243, 81257, 81329, 81443*) are considered investigational for all other indications. *Fragile X (81243) and spinal muscular atrophy (SMA) (81329) carrier screening may be billed along with 81443 if performed separately from the remainder of the panel per CPT Code Book Guidelines. back to top BASIC CARRIER SCREENING PANELS (Cystic fibrosis, Spinal Muscular Atrophy, Fragile X, Hemoglobinopathies, not more than 14 genes) Basic carrier screening panels (CFTR, SMN1/2, FMR1, HBB/HBA1/HBA2, but not more than 14 genes) (81220, 81329, 81243, 81257) should be evaluated not as a panel, but by the individual test criteria described in this policy, including but not limited to: I. Cystic fibrosis carrier screening Spinal muscular atrophy carrier screening II. III. Fragile X syndrome carrier screening IV. Hemoglobinopathy carrier screening back to top CYSTIC FIBROSIS CARRIER SCREENING CFTR Known Familial Variant Analysis I. Cystic fibrosis carrier screening via CFTR targeted mutation analysis for a known familial mutation (81221) may be considered medically necessary when: 6 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant in CFTR. II. Cystic fibrosis carrier screening via CFTR targeted mutation analysis for a known familial mutation (81221) is considered investigational for all other indications. CFTR Sequencing, Deletion/Duplication Analysis, or Mutation Panel I. Cystic fibrosis carrier screening via CFTR sequencing (81223), deletion/duplication analysis (81222), or a mutation panel (81220) using at a minimum the ACMG-23 variant panel, may be considered medically necessary when: A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, OR B. The member’s/enrollee’s reproductive partner is a known carrier for cystic fibrosis. II. Cystic fibrosis carrier screening via CFTR sequencing (81223), deletion/duplication analysis (81222), or a mutation panel (81220) using at a minimum the ACMG-23 variant panel, is considered investigational for all other indications. CFTR Intron 9 PolyT and TG Analysis (previously called Intron 8 polyT/TG Analysis) I. Analysis of the CFTR intron 9 polyT and TG regions (81224) for cystic fibrosis carrier screening may be considered medically necessary when: A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member/enrollee is known to have an R117H variant in the CFTR gene. II. Analysis of the CFTR intron 9 polyT and TG regions (81224) for cystic fibrosis carrier screening is considered investigational for all other indications. Note: Refer to Genetic Testing for Multisystem Inherited Disorders, Intellectual Disability and Developmental Delay for coverage criteria for genetic testing to establish a diagnosis of cystic fibrosis. back to top 7 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 SPINAL MUSCULAR ATROPHY CARRIER SCREENING SMN1 Targeted Variant Analysis I. Spinal muscular atrophy (SMA) carrier screening via SMN1 targeted variant analysis (81337, 81403) may be considered medically necessary when: A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant in SMN1. II. Spinal muscular atrophy (SMA) carrier screening via SMN1 targeted variant analysis (81337, 81403) is considered investigational for all other indications. SMN1 Sequencing and/or Deletion/Duplication and SMN2 Deletion/Duplication Analysis I. Spinal muscular atrophy (SMA) carrier screening via SMN1 sequencing and/or deletion/duplication analysis and SMN2 deletion/duplication analysis (81329, 81336, 81401, 81405) is considered medically necessary when: A. The member/enrollee and/or member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, OR B. The member’s/enrollee’s reproductive partner is a known carrier for spinal muscular atrophy. II. Spinal muscular atrophy (SMA) carrier screening via SMN1 sequencing and/or deletion/duplication analysis and SMN2 deletion/duplication analysis (81329, 81336, 81401, 81405) is considered investigational for all other indications. Note: Refer to Genetic Testing for Epilepsy, Neuromuscular, and Neurodegenerative Disorders for coverage criteria for genetic testing to establish a diagnosis of spinal muscular atrophy (SMA). back to top 8 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 FRAGILE X SYNDROME CARRIER SCREENING FMR1 Repeat Analysis I. Fragile X carrier screening via FMR1 CGG-trinucleotide repeat analysis (81243, 81244) may be considered medically necessary when: A. The member/enrollee has been diagnosed with premature ovarian insufficiency or elevated follicle-stimulating hormone level before age 40 years, OR B. The member/enrollee is considering a pregnancy or is currently pregnant, AND 1. The member/enrollee has one of the following: a) Close relative with Fragile X syndrome (i.e., close relative has more than 200 CGG repeats in the FMR1 gene), OR b) Close relative who is a known carrier for Fragile X syndrome (i.e., close relative has between 55-200 CGG repeats in the FMR1 gene), OR c) Close relative with unexplained intellectual disability, developmental delay, or autism spectrum disorder, OR d) Close relative diagnosed with premature ovarian insufficiency or elevated follicle-stimulating hormone level before age 40 years. II. Fragile X carrier screening via FMR1 CGG-trinucleotide repeat analysis (81243, 81244) is considered investigational for all other indications. Note: Refer to Genetic Testing for Multisystem Inherited Disorders, Intellectual Disability and Developmental Delay for coverage criteria for genetic testing to establish a diagnosis of fragile X syndrome. back to top HEMOGLOBINOPATHY CARRIER SCREENING HBA1, HBA2, or HBB Targeted Variant Analysis I. Hemoglobinopathy carrier screening via HBA1, HBA2 (81257, 81258), or HBB (81361, 81362) targeted variant analysis may be considered medically necessary when: 9 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member/enrollee meets one of the following: 1. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant in HBA1, HBA2, or HBB, OR 2. The member’s/enrollee’s reproductive partner is a known carrier of a pathogenic or likely pathogenic variant in HBA1, HBA2, or HBB, OR 3. The member’s/enrollee’s reproductive partner is known to have a diagnosis of a hemoglobinopathy, OR 4. The member’s/enrollee’s hematologic screening results (e.g., MCV, MCH, CBC, hemoglobin electrophoresis, or dichlorophenol indophenol (DCIP)) are suggestive of or do not conclusively rule out a hemoglobinopathy. II. Hemoglobinopathy carrier screening via HBA1, HBA2 (81257, 81258), or HBB (81361, 81362) targeted variant analysis is considered investigational for all other indications. HBA1, HBA2, or HBB Sequencing and/or Deletion/Duplication Analysis I. Hemoglobinopathy carrier screening via HBA1, HBA2 (81259, 81269), or HBB (81363, 81364) sequencing and/or deletion/duplication analysis may be considered medically necessary when: A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member’s/enrollee’s hematologic screening results (e.g., MCV, MCH, CBC, hemoglobin electrophoresis, or dichlorophenol indophenol (DCIP)) are suggestive of, or do not conclusively rule out, a hemoglobinopathy. II. Hemoglobinopathy carrier screening via HBA1, HBA2 (81259, 81269), or HBB (81363, 81364) sequencing and/or duplication analysis is considered investigational for all other indications. Note: Refer to Genetic Testing for Hematologic Disorders (non-cancerous) for coverage criteria for genetic testing to establish a diagnosis of a hemoglobinopathy. back to top 10 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 ASHKENAZI JEWISH CARRIER PANEL TESTING I. Ashkenazi Jewish carrier panel testing (81412) may be considered medically necessary when: A. The member/enrollee and/or the member’s/enrollee’s reproductive partner is considering pregnancy or is currently pregnant, AND B. The member/enrollee is of Ashkenazi Jewish ancestry, AND C. The panel includes, at a minimum, screening for carrier status for genetic conditions associated with the following genes, as recommended by the American College of Medical Genetics (ACMG): 1. Tay Sachs disease (HEXA) 2. Canavan disease (ASPA) 3. Cystic fibrosis (CFTR) 4. Familial dysautonomia (ELP1) 5. Bloom syndrome (BLM) 6. Fanconi anemia (FANCC) 7. Niemann-Pick disease (SMPD1) 8. Gaucher disease (GBA) 9. Mucolipidosis IV (MCOLN1) Note: If only one partner is of Ashkenazi Jewish ancestry, then testing of that partner is considered medically necessary. Testing of the other partner is considered medically necessary only if the result of testing of the Ashkenazi Jewish partner is positive. back to top DUCHENNE AND BECKER MUSCULAR DYSTROPHY CARRIER SCREENING DMD Targeted Variant Analysis I. Duchenne and Becker muscular dystrophy carrier screening via DMD targeted variant analysis (81408, 81403) may be considered medically necessary when: A. The member/enrollee is considering pregnancy or is currently pregnant, AND B. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant in DMD. 11 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 II. Duchenne and Becker muscular dystrophy carrier screening via DMD targeted variant analysis (81408, 81403) is considered investigational for all other indications. DMD Sequencing and/or Deletion/Duplication Analysis I. Duchenne and Becker muscular dystrophy carrier screening via DMD sequencing and/or deletion/duplication analysis (81161, 81408, 0218U) may be considered medically necessary when: A. The member/enrollee is considering pregnancy or is currently pregnant, AND B. The member/enrollee has one of the following: 1. First- or second-degree male relative diagnosed with Duchenne or Becker muscular dystrophy. II. Duchenne and Becker muscular dystrophy carrier screening via DMD sequencing and/or deletion/duplication analysis (81161, 81408, 0218U) is considered investigational for all other indications. Note: Refer to Genetic Testing for Epilepsy, Neuromuscular, and Neurodegenerative Disorders for coverage criteria for genetic testing to establish a diagnosis of Duchenne or Becker muscular dystrophy. back to top GENERAL CRITERIA FOR TARGETED CARRIER SCREENING NOTE: Each section in the policy reference table includes specific coverage criteria. For any prenatal or preconception carrier screening test that does not have specific criteria above, refer to the following coverage criteria to assess for medical necessity. Targeted carrier screening is defined as a test that screens for a known mutation in one gene associated with a specific genetic condition. I. Carrier screening for a genetic disorder (81174, 81190, 81200, 81205, 81209, 81242, 81247, 81248, 81250, 81251, 81253, 81254, 81289, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408) may be considered medically necessary when: A. The member/enrollee is considering pregnancy or is currently pregnant, AND B. The genetic disorder is a recessive condition with a childhood onset, AND C. One of the following: 12 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 1. The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant associated with the disorder, OR 2. The member’s/enrollee’s reproductive partner is a carrier for the genetic disorder, OR 3. The member/enrollee or the member’s/enrollee’s reproductive partner are members of a population known to have a carrier rate of 1% or higher for the genetic condition, OR 4. The member/enrollee or the member’s/enrollee’s reproductive partner has a first- or second-degree relative who is affected with the genetic disorder. II. Carrier screening for a genetic disorder (81174, 81190, 81200, 81205, 81209, 81242, 81247, 81248, 81250, 81251, 81253, 81254, 81289, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408) is considered investigational when the member/enrollee does not meet any criteria above. back to top NOTES AND DEFINITIONS 1. Close relatives include first, second, and third degree relatives on the same side of the family: a. First-degree relatives are parents, siblings, and children b. Second-degree relatives are grandparents, aunts, uncles, nieces, nephews, grandchildren, and half siblings c. Third-degree relatives are great grandparents, great aunts, great uncles, great grandchildren, and first cousins. CLINICAL CONSIDERATIONS “Negative” carrier screening results reduce, but do not eliminate, the chance of an individual being a carrier for the condition(s) screened. Therefore, there is still a “residual risk” of being a carrier for the condition(s) screened. The residual risk is the chance that the individual is still a carrier based on a normal/negative carrier screen. The residual risk will vary depending on 13 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 which test is performed, how many mutations are included for each condition, the patient’s ethnicity, etc. It is important to recognize that family history, ethnicity, and race are self-reported, and may not be completely accurate, particularly in multi-ethnic and multi-racial societies. When one member of a couple is at high risk of being a carrier for a certain condition due to ancestry (e.g., Ashkenazi Jewish, French-Canadian, Cajun, etc.) or has a family history of a condition, the high-risk partner should be offered screening. If the high-risk partner is found to be a carrier, the other partner should then be offered screening. Genetic counseling is strongly recommended for patients considering expanded carrier screening. BACKGROUND AND RATIONALE Expanded Carrier Screening Panels American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists (ACOG) published practice bulletin No. 690 (2017, reaffirmed 2020) regarding “Carrier Screening in the Age of Genomic Medicine”, which made the following recommendations: “Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for pre pregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.” (page e95) It was also recommended that: “All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies.” (p. e95) American College of Medical Genetics and Genomics (ACMG), American College of Obstetricians and Gynecologists (ACOG), the National Society of Genetic Counselors (NSGC), the Perinatal Quality Foundation, and the Society of Maternal-Fetal Medicine (SMFM) The American College of Medical Genetics and Genomics (ACMG), ACOG, the National Society of Genetic Counselors (NSGC), the Perinatal Quality Foundation, and the Society of Maternal-Fetal Medicine (SMFM) published a commentary discussing expanded carrier screening in 2015 stating that “...women of reproductive age should ideally be offered carrier screening before conception.” (p. 657) 14 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 American College of Medical Genetics and Genomics (ACMG): ACMG published a practice resource (2021) regarding screening for autosomal recessive and X- linked conditions during pregnancy and preconception, which includes the following recommendations: ● The phrase “expanded carrier screening” be replaced by “carrier screening”. ● Adopting a more precise tiered system based on carrier frequency (p. 1796) ○ Tier 1: CF + SMA + Risk Based Screening ○ ○ Tier 2: 1/100 carrier frequency or higher (includes Tier 1) Tier 3: 1/200 carrier frequency or higher (includes Tier 2) includes X- linked conditions Tier 4: 1/200 carrier frequency or higher (includes Tier 3) genes/condition will vary by lab ○ ● All pregnant patients and those planning a pregnancy should be offered Tier 3 carrier screening. (p. 1797) Tier 4 screening should be considered (p. 1797): ● ○ When a pregnancy stems from a known or possible consanguineous relationship (second cousins or closer) When a family or personal medical history warrants. ○ ● Reproductive partners of pregnant patients and those planning a pregnancy may be offered Tier 3 carrier screening for autosomal recessive conditions when carrier screening is performed simultaneously with their partner." ACMG does not recommend (p. 1797): ● Offering Tier 1 and/or Tier 2 screening without Tier 3, because these do not provide equitable evaluation of all racial/ethnic groups. Routine offering of Tier 4 panels. ● Basic Carrier Screening Panels (Cystic Fibrosis, Spinal Muscular Atrophy, Fragile X, Hemoglobinopathies, not more than 14 genes) American College of Obstetricians and Gynecologists (ACOG) ACOG published practice bulletin No. 691 (March 2017, reaffirmed 2020) and following recommendations related to carrier screening (p. 2): ● Screening for spinal muscular atrophy should be offered to all individuals who are considering pregnancy or are currently pregnant. 15 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 ● ● ● Cystic fibrosis carrier screening should be offered to all individuals who are considering pregnancy or are currently pregnant. Fragile X premutation carrier screening is recommended for patients with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome and who are considering pregnancy or are currently pregnant. A complete blood count with red blood cell indices should be performed in all individuals who are currently pregnant to assess not only their risk of anemia but also to allow assessment for risk of a hemoglobinopathy. Ideally, this testing also should be offered to women before pregnancy. A hemoglobin electrophoresis should be performed in addition to a complete blood count if there is suspicion of hemoglobinopathy based on ethnicity (African, Mediterranean, Middle Eastern, Southeast Asian, or West Indian descent). If red blood cell indices indicate a low mean corpuscular hemoglobin or mean corpuscular volume, hemoglobin electrophoresis also should be performed. ACOG published practice bulletin No. 690 (March 2017, reaffirmed 2020) and following recommendations related to carrier screening (p. 1): All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. Fragile X premutation carrier screening is recommended for women with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome, or women with a personal history of ovarian insufficiency. Additional screening also may be indicated based on family history or specific ethnicity. Cystic Fibrosis Carrier Screening CFTR Known Familial Analysis ACOG published practice bulletin No. 691 (March 2017, reaffirmed 2020) and the following recommendations related to carrier screening: When both partners are unaffected, but one or both has a family history of cystic fibrosis - Genetic counseling and medical record review should be performed to determine if CFTR mutation analysis in the affected family member is available. Carrier screening should be offered for both partners, with attention to ensure that the familial mutation is included in the assessment. (p. 7) CFTR Sequencing and/or Deletion/Duplication Analysis, or Mutation Panel National Society of Genetic Counselors (NSGC) 16 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 NSGC published recommendations in 2013 addressing carrier screening for cystic fibrosis. It is recommended that: “Carrier testing for CF [cystic fibrosis] should be offered to all women of reproductive age, regardless of ancestry; preferably pre-conceptionally. CF carrier testing should also be offered…to partners of mutation carriers...” (p. 8) American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists (ACOG) published practice bulletin No. 691 (2017, reaffirmed 2020) regarding “Carrier Screening Genetic Conditions”, which made the following recommendations for cystic fibrosis carrier screening: ● Cystic fibrosis carrier screening should be offered to all women who are considering pregnancy or are currently pregnant. (p. 1) American College of Medical Genetics and Genomics (ACMG) In 2001, ACMG made the following recommendation (Grody et al, 2001) : ● The Committee recommends that CF carrier screening be offered to non-Jewish Caucasians and Ashkenazi Jews, and made available to other ethnic and racial groups who will be informed of their detectability through educational brochures, the informed consent process, and/or other efficient methods. For example, Asian-Americans and Native-Americans without significant Caucasian admixture should be informed of the rarity of the disease and the very low yield of the test in their respective populations. Testing should be made available to African-Americans, recognizing that only about 50% of at-risk couples will be detected. An educational brochure and a consent form which recites this information as well as a sign-off for those choosing not to be tested after reading these materials is being prepared by the Working Group on Patient Education and Informed Consent. (p. 150) ● We recommend that preconception testing be encouraged whenever possible, although we recognize that for practical purposes, testing will often occur in the prenatal setting.” (p. 150) ● The Committee recommends that the R117H mutation be included in the test panel, while recognizing that this will screen for male infertility as well as CF. Thus, to distinguish the genotypes of R117H associated with CF from that associated with CBAVD, reflex testing for the 5T/7T/9T variant is recommended only when the R117H mutation is positive. (p. 151) In their 2020 technical standard for CFTR variant testing, the American College of Medical Genetics and Genomics (ACMG) recommends a minimum number of mutations tested in the CFTR gene if carrier testing is pursued: “For those laboratories who wish to continue using a 17 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 targeted testing approach, the ACMG-23 variant panel remains as the minimum list of CFTR variants that should be included.” (p. 5) “The development of the ACMG-23 variant panel followed a careful analysis and revision of the original ACMG-25 variant panel, which was a product of two National Institutes of Health (NIH) consensus conferences (1997 and 1998), followed by a Steering Committee made up of ACMG and ACOG representatives. This was the first time professional organizations recommended population-based screening at the DNA level for a genetic condition. CFTR Intron 9 PolyT and TG Analysis (previously called Intron 8 polyT/TG Analysis) American College of Medical Genetics and Genomics (ACMG), 2002 Per the ACMG Laboratory Quality Assurance (QA) Committee, they recommend that all R117H positive results require reflex testing for the 5T/7T/9T variant in the polythymidine tract at intron 8 in CFTR gene. (Page 389) Spinal Muscular Atrophy Carrier Screening SMN1 Targeted Variant Analysis American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists (ACOG) published practice bulletin No. 691 (2017) regarding “Carrier Screening for Genetic Conditions”, which made the following recommendations (p. 597 to 598): When an individual is found to be a carrier for a genetic condition, the individual’s relatives are at risk of carrying the same mutation. Individuals with a positive family history of a genetic condition should be offered carrier screening for the specific condition and may benefit from genetic counseling. SMN1 Sequencing and/or Deletion/Duplication and SMN2 Deletion/Duplication Analysis American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists (ACOG) published practice bulletin No. 691 (March 2017, reaffirmed 2020) and the following recommendations (p. 2): ● Screening for spinal muscular atrophy should be offered to all women who are considering pregnancy or are currently pregnant. 18 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 ● In patients with a family history of spinal muscular atrophy, molecular testing reports of the affected individual and carrier testing of the related parent should be reviewed, if possible, before testing. If the reports are not available, SMN1 deletion testing should be recommended for the low-risk partner. American College of Medical Genetics and Genomics (ACMG) The American College of Medical Genetics and Genomics recommended the following on carrier screening for spinal muscular atrophy (Prior, et al, 2008): Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity. Ideally, the testing should be offered before conception or early in pregnancy. The primary goal is to allow carriers to make informed reproductive choices. (p. 841) Fragile X Syndrome Carrier Screening - FMR1 Repeat Analysis American College of Obstetricians and Gynecologists (ACOG) The American College of Obstetricians and Gynecologists (ACOG) published practice bulletin No. 691 (2017) regarding “Carrier Screening for Genetic Conditions”, which made the following recommendations (p. 2): ● ● ● ● ● Fragile X premutation carrier screening is recommended for women with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome and who are considering pregnancy or are currently pregnant. If a woman has unexplained ovarian insufficiency or failure or an elevated follicle- stimulating hormone level before age 40 years, fragile X carrier screening is recommended to determine whether she has an FMR1 premutation. All identified individuals with intermediate results and carriers of a fragile X premutation or full mutation should be provided follow-up genetic counseling to discuss the risk to their offspring of inheriting an expanded full-mutation fragile X allele and to discuss fragile X-associated disorders (premature ovarian insufficiency and fragile X tremor/ataxia syndrome). Prenatal diagnostic testing for fragile X syndrome should be offered to known carriers of the fragile X premutation or full mutation. DNA-based molecular analysis (eg, Southern blot analysis and polymerase chain reaction) is the preferred method of diagnosis of fragile X syndrome and of determining FMR1 triplet repeat number (eg, premutations). In rare cases, the size of the triplet repeat and the methylation status do not correlate, which makes it difficult to predict the clinical phenotype. In cases of this discordance, the patient should be referred to a genetics professional. 19 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 American College of Medical Genetics and Genomics (ACMG) ACMG published practice guidelines for carrier screening for Fragile X syndrome (2005), which recommended that Fragile X syndrome carrier testing should be offered to individuals with the following: ● Individuals seeking reproductive counseling who have (a) a family history of fragile X syndrome or (b) a family history of undiagnosed mental retardation. ● Women who are experiencing reproductive or fertility problems associated with elevated follicle stimulating hormone (FSH) levels, especially if they have (a) a family history of premature ovarian failure, (b) a family history of fragile X syndrome, or (c) male or female relatives with undiagnosed mental retardation. (p. 586) Hemoglobinopathy Carrier Screening - HBA1, HBA2, or HBB Sequencing and/or Deletion/Duplication Analysis American College of Obstetricians and Gynecologists (ACOG) ACOG published practice bulletin No. 691 (March 2017, reaffirmed 2020) and following recommendations related to carrier screening (p. 2): ● A complete blood count with red blood cell indices should be performed in all women who are currently pregnant to assess not only their risk of anemia but also to allow assessment for risk of a hemoglobinopathy. Ideally, this testing also should be offered to women before pregnancy. A hemoglobin electrophoresis should be performed in addition to a complete blood count if there is suspicion of hemoglobinopathy based on ethnicity (African, Mediterranean, Middle Eastern, Southeast Asian, or West Indian descent). If red blood cell indices indicate a low mean corpuscular hemoglobin or mean corpuscular volume, hemoglobin electrophoresis also should be performed. ● Ashkenazi Jewish Carrier Panel Testing American College of Obstetricians and Gynecologists (ACOG) and American College of Medical Genetics and Genomics (ACMG) ACMG and ACOG published practice guidelines for carrier screening in individuals of Ashkenazi Jewish descent (2008) which made the following recommendations: 20 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 ● We recommend that carrier screening for cystic fibrosis, Canavan disease, familial dysautonomia, and Tay-Sachs disease be offered to all Ashkenazi Jews who are pregnant or considering pregnancy, according to current American College of Medical Genetics and/or the American College of Obstetricians and Gynecologists (ACOG) guidelines. In addition, we recommend that carrier screening be offered for Fanconi anemia (Group C), Niemann-Pick (Type A), Bloom syndrome, mucolipidosis IV, and Gaucher disease. Carrier screening for these disorders should include testing for the specific mutations listed [in Table 1], which will result in a carrier detection rate 95% for most disorders. As a result, even in disorders that are relatively less common, expected mutation-specific carrier frequencies are relatively high. ● If only one member of a couple is of Ashkenazi Jewish background, testing should still be offered. Ideally, the Jewish member of the couple should be tested first. If the Jewish partner has a positive test result, the other partner (regardless of background) should be screened for that particular disorder. In the case of Tay-Sachs disease, testing can be performed using the biochemical assay, which has an excellent detection rate regardless of ethnic or racial background. The mutation detection rate and carrier frequency among different ethnic/racial groups is known for cystic fibrosis; however, for the other disorders, a discussion should include the lack of a precise residual risk in the case where the non-Jewish partner is negative on mutation analysis. ● Generally, individuals self-identify themselves as Jewish and whether or not they are of eastern European origin. One Jewish grandparent is sufficient to offer testing. However, if someone is unsure as to their precise lineage, it is recommended to offer testing. At this time, there is no specific panel of tests available for Jews from non-Ashkenazi background. However, a proper family history and ethnic origin should still be obtained and appropriate testing offered (e.g., hemoglobinopathy screening for those from the Mediterranean basin). ● In the case where someone is identified as a carrier, genetic counseling should be readily available to discuss the findings and possible reproductive options. Furthermore, a discussion regarding the importance of genetic counseling for other family members should be stressed. Although the provider cannot contact family members directly, the individual should be encouraged to discuss the findings with his or her family if possible and appropriate. (p. 54 to 56) American College of Obstetricians and Gynecologists (ACOG) ACOG published practice bulletin No. 691 (March 2017, reaffirmed 2020) and following recommendations related to carrier screening (p. 3): When only one partner is of Ashkenazi Jewish descent, that individual should be offered screening first. If it is determined that this individual is a carrier, the other partner should be offered screening. However, the couple should be informed that the carrier frequency and the detection rate in non-Jewish individuals are unknown for most of these disorders, 21 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 except for Tay–Sachs disease and cystic fibrosis. Therefore, it is difficult to accurately predict the couple’s risk of having a child with the disorder. Duchenne and Becker Muscular Dystrophy Carrier Screening DMD Targeted Variant Analysis GeneReviews: Dystrophinopathies GeneReviews is an expert-authored review of current literature on a genetic disease and goes through a rigorous editing and peer review process before being published online. The recommendation for DMD testing strategy is as follows: Because the majority of pathogenic variants involve deletions of one or more exons, gene- targeted deletion/duplication analysis of DMD is performed first and followed by sequence analysis if no pathogenic variant is found. DMD Sequencing and/or Deletion/Duplication Analysis European Molecular Genetics Quality Network (EMQN) EMQN published best practice guidelines for genetic testing in dystrophinopathies (2020), which included the following in regard to carrier testing in females (p. 1147): ● When the familial pathogenic variant is known, carrier testing should be undertaken by ● specific testing for this variant. When the familial pathogenic variant is unknown and an affected male is not available to be tested, female relatives at risk of being carriers should be offered the full cohort of level 1 and 2 genetic testing (i.e. CNV analysis and sequencing) since these two approaches are cost effective and offer ~99% sensitivity. General Criteria for Targeted Carrier Screening American College of Obstetricians and Gynecologists (ACOG) ACOG published practice bulletin No. 690 (March 2017, reaffirmed 2020) and following recommendations related to carrier screening: ● Given the multitude of conditions that can be included in expanded carrier screening 22 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 panels, the disorders selected for inclusion should meet several of the following consensus-determined criteria: have a carrier frequency of 1 in 100 or greater, have a well-defined phenotype, have a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life. Additionally, screened conditions should be able to be diagnosed prenatally and may afford opportunities for antenatal intervention to improve perinatal outcomes, changes to delivery management to optimize newborn and infant outcomes, and education of the parents about special care needs after birth. ● Carrier screening panels should not include conditions primarily associated with a disease of adult onset. (p. e36) ACOG published practice bulletin No. 691 (March 2017) and following recommendations related to carrier screening ● Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. Information about carrier screening should be provided to every pregnant woman. Carrier screening and counseling ideally should be performed before pregnancy because this enables couples to learn about their reproductive risk and consider the most complete range of reproductive options. A patient may decline any or all screening. When an individual is found to be a carrier for a genetic condition, his or her relatives are at risk of carrying the same mutation. The patient should be encouraged to inform his or her relatives of the risk and the availability of carrier screening. If an individual is found to be a carrier for a specific condition, the patient’s reproductive partner should be offered testing in order to receive informed genetic counseling about potential reproductive outcomes. If both partners are found to be carriers of a genetic condition, genetic counseling should be offered. (p. 597) ● ● ● ● ● National Society of Genetic Counselors (NSGC): The National Society of Genetic Counselors updated a position statement (2018) regarding the genetic testing of minors for adult-onset conditions, stating the following: [NSGC] encourages deferring predictive genetic testing of minors for adult-onset conditions when results will not impact childhood medical management or significantly benefit the child. Predictive testing should optimally be deferred until the individual has the capacity to weigh the associated risks, benefits, and limitations of this information, taking his/her circumstances, preferences, and beliefs into account to preserve his/her autonomy and right to an open future. back to top 23 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 Reviews, Revisions, and Approvals Policy developed REFERENCES Revision Date 03/23 Approval Date 03/23 1. Langfelder-Schwind E, Karczeski B, Strecker MN, et al. Molecular Testing for Cystic Fibrosis Carrier Status Practice Guidelines: Recommendations of the National Society of Genetic Counselors. J Genet Couns. 2014;23(1):5-15. doi:10.1007/s10897-013-9636-9 2. Deignan JL, Astbury C, Cutting GR, et al. CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(8):1288-1295. doi:10.1038/s41436-020-0822-5 3. “Genetic Testing of Minors for Adult-Onset Condition”. Position Statement from National Society for Genetic Counselors. https://www.nsgc.org/Policy-Research-and- Publications/Position-Statements/Position-Statements/Post/genetic-testing-of-minors-for- adult-onset- conditions#:~:text=The%20National%20Society%20of%20Genetic,or%20significantly% 20benefit%20the%20child. Released October 9, 2018. Updated June 26, 2019. 4. Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol. 2017;129(3):e35-e40. doi:10.1097/AOG.0000000000001951 5. Committee Opinion No. 691 Summary: Carrier Screening for Genetic Conditions. Obstet Gynecol. 2017;129(3):597-599. doi:10.1097/AOG.0000000000001948 6. Gregg AR, Aarabi M, Klugman S, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG) [published online ahead of print, 2021 Jul 20] [published correction appears in Genet Med. 2021 Aug 27;:]. Genet Med. 2021;10.1038/s41436-021-01203-z. doi:10.1038/s41436-021-01203-z 7. Edwards JG, Feldman G, Goldberg J, et al. Expanded Carrier Screening in Reproductive Medicine—Points to Consider. Obstet Gynecol. 2015;125(3):653-662. doi:10.1097/AOG.0000000000000666 8. Gross SJ, Pletcher BA, Monaghan KG; Professional Practice and Guidelines Committee. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. 2008;10(1):54- 56. doi:10.1097/GIM.0b013e31815f247c 9. Prior TW; Professional Practice and Guidelines Committee. Carrier screening for spinal muscular atrophy. Genet Med. 2008;10(11):840-842. doi:10.1097/GIM.0b013e318188d069 10. Darras BT, Urion DK, Ghosh PS. Dystrophinopathies. 2000 Sep 5 [Updated 2022 Jan 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. 24 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 Seattle (WA): University of Washington, Seattle; 1993-20230. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1119/ 11. Fratter C, Dalgleish R, Allen SK, et al. EMQN best practice guidelines for genetic testing in dystrophinopathies. Eur J Hum Genet. 2020;28(9):1141-1159. doi:10.1038/s41431- 020-0643-7 12. Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005;7(8):584-587. doi:10.1097/01.gim.0000182468.22666.dd 13. Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med. 2001;3(2):149-154. doi:10.1097/00125817-200103000-00010 back to top Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. 25 Concert Genetic Testing: Prenatal and Preconception Carrier Screening V2.2023 Date of Last Revision: 3/1/2023 This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members/enrollees. This clinical policy is not intended to recommend treatment for members/enrollees. Members/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members/enrollees and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. 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