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Genetic Carrier Screening related to Cystic Fibrosis and SMA

Policy Number: MP-710

Latest Review Date: September 2021

Category: Laboratory

Policy Grade: B


Carrier testing for the genetic diseases SMA (spinal muscular atrophy) and/or CF (cystic fibrosis) may be considered medically necessary when the following criteria is met:

  • Individuals must be of reproductive age; AND
  • Individuals must have potential and intention to reproduce; AND
  • One or both individuals have the genetic disorder; OR
    • One or both individuals already have a child with the genetic disorder; OR
    • One or both individuals have a family history of the genetic disorder; OR
    • One or both individuals belong to an ethnic group that has a high rate of carriers of certain genetic disorders (e.g. Ashkenazi Jews); OR
    • One or both individuals have a family history of congenital bilateral absence of the vas deferens (for cystic fibrosis carrier screening)

Carrier screening for the general population is considered not medically necessary.


Carrier screening is performed to detect genetic mutations that may increase the risk of a genetic disorder. This testing may impact the reproductive decision-making for parents or prospective parents.

Carrier Screening may be available for autosomal recessive conditions, autosomal dominant less penetrant conditions, X-linked conditions, and certain chromosome abnormalities. In general, Carrier Screening may be performed for conditions that are found in the general population (pan-ethnic), for diseases that are more common in a particular population, or based on family history. For individuals of Ashkenazi Jewish descent (Gross et al., 2008), certain autosomal recessive conditions are more prevalent and many of these disorders are lethal in childhood or associated with significant morbidity.

A carrier of a genetic disorder has one abnormal allele for a disorder. When associated with an autosomal recessive or X-linked disorder, carriers of the causative mutation are typically unaffected. When associated with an autosomal dominant disorder, the individual has one normal and one mutated copy of the gene and may be affected with the disorder, may be unaffected but at high risk of developing the disease later in life, or the carrier may remain unaffected because of the sex-limited nature of the disease. Homozygous-affected offspring (those who inherit the mutation from both parents) manifest the disease.


This policy is based on an evidence review most recently performed on September 10, 2021.

Summary of Evidence

The clinical utility of carrier testing is in how the results of the diagnostic test will have an impact on management decisions and health outcomes. Changes in management will involve decisions on family planning. The results of genetic testing can be used to assist individuals with reproductive decisions such as avoidance of pregnancy, preimplantation genetic testing, adoption, etc. The beneficial health outcome would be a reduction in the prevalence of severe, recessive inherited disorders among live births in patients who get tested. For tests that have high accuracy in detecting pathologic mutations, and very low false-positive rates, it is likely that use of the test will reduce the number of births with the inherited disorder. The magnitude of benefit will depend on the frequency of the disorder and the sensitivity of the test in detecting mutations that are present. Carrier testing should be performed for diseases that have high penetrance and do not have (a highly) variable expression. Carrier testing is only appropriate when the individual(s) are planning a pregnancy or are currently pregnant.

Practice Guidelines and Position Statements

American College of Medical Genetics and Genomics (ACMG) & American College of Obstetricians and Gynecologists (ACOG)

An ACMG position statement states that although some commercial laboratories offer expanded carrier screening panels, there is little consensus on which disease genes and mutations to include in these panels (Grody et al., 2013; Edwards et al., 2015). Panels that include multiple carrier screening tests may be useful if they include the diseases that are present with increased frequency in a specific population (i.e., Ashkenazi Jewish Carrier Screening), but do not have clinical utility when they include a larger number of genetic diseases for which the individual does not have an increased risk of being a carrier.

Guidelines from the American College of Medical Genetics (ACMG, 2008) and the American College of Obstetricians and Gynecologists (ACOG, 2009) agree that carrier testing is indicated for adults with a family history of SMA.

U.S. Preventive Services Task Force

Not applicable.


SMA, Spinal Muscular Atrophy, CF, Cystic Fibrosis, Carrier Screening


Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.


Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.


CPT codes:


CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; common variants (e.g., ACMG/ACOG guidelines)


CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; known familial variants


CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; duplication/deletion variants


CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; full gene sequence


CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; intron 8 poly-T analysis (e.g., male infertility)


SMN1 (survival of motor neuron 1, telomeric) (e.g., spinal muscular atrophy) gene analysis; full gene sequence


SMN1 (survival of motor neuron 1, telomeric) (e.g., spinal muscular atrophy) gene analysis; known familial sequence variant(s)


SMN1 (survival of motor neuron 1, telomeric) (e.g., spinal muscular atrophy) gene analysis; dosage/deletion analysis (e.g., carrier testing), includes SMN2 (survival of motor neuron 2, centromeric) analysis, if performed


Genetic testing for severe inherited conditions (e.g., cystic fibrosis, Ashkenazi Jewish-associated disorders [e.g., Bloom syndrome, Canavan disease, Fanconi anemia type C, mucolipidosis type VI, Gaucher disease, Tay-Sachs disease], beta hemoglobinopathies, phenylketonuria, galactosemia), genomic sequence analysis panel, must include sequencing of at least 15 genes (e.g., ACADM, ARSA, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GBA, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH)


Unlisted molecular pathology procedure


Unlisted multianalyte assay with algorithmic analysis


  1. American College of Obstetricians and Gynecologists. Committee Opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017 Mar; 129(3):595-596. Reaffirmed 2019a.
  2. American College of Obstetrics and Gynecologists. Committee Opinion No. 691: Carrier screening for genetic conditions. Obstetrics and Gynecology. Mar 2017; 129(3):e41-e55. Reaffirmed 2019b.
  3. American College of Obstetrics and Gynecology (ACOG) Committee on Genetics. Committee opinion No. 432: spinal muscular atrophy. Obstet Gynecol. 2009; 113:1194-6.
  4. Arjunan A, Litwack K, Collins N, Charrow J. Carrier screening in the era of expanding genetic technology. Genet Med. 2016 Dec; 18(12):1214-1217.
  5. Edwards JG, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine-points to consider a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol 2015; 125:653–62.
  6. Ghiossi CE, Goldberg JD, Haque IS, et al. Clinical utility of expanded carrier screening: reproductive behaviors of at-risk couples. J Genet Couns. 2017 Sep 27.
  7. Grody WW, Thompson BH, Gregg AR, et al. ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med. 2013 Jun; 15(6):482-3.
  8. Gross SJ, Pletcher BA, Monaghan KG, et al. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. 2008 Jan; 10(1):54-6, reaffirmed 2013.
  9. Haque IS, Lazarin GA, Kang HP, et al. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA. 2016 Aug 16; 316(7):734-42.
  10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  11. Johansen Taber KA, Beauchamp KA, Lazarin GA, et al. Clinical utility of expanded carrier screening: results-guided actionability and outcomes. Genet Med. 2018 Oct 11.
  12. McGraw-Hill Concise Dictionary of Modern Medicine. Test panel. (2002). Retrieved May 29 2019 from
  13. Medicare Claims Processing Manual Chapter 16 - Laboratory Services January 11, 2019. Accessed May 29, 2019.
  14. Peyser A, Singer T, Mullin C, et al. Comparing ethnicity-based and expanded carrier screening methods at a single fertility center reveals significant differences in carrier rates and carrier couple rates. Genet Med 2018 Oct 16.
  15. Prior T. For the Professional Practice and Guidelines Committee of American College of Medical Genetics ACMG. Carrier screening for spinal muscular atrophy. Genet Med. 2008; 10(11):840-2.
  16. Shi L, Webb BD, Birch AH, et al. Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants. Clinical genetics. 2017; 91(4):599-604.
  17. Shraga R, Yarnall S, Elango S, et al. Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening. BMC Genetics. (2017) 18:99.
  18. Terhaar C, Teed N, Allen R, et al. Clinical experience with multigene carrier panels in the reproductive setting. Prenat Diagn. 2018 Apr 23.
  19. Wilfond BS, Kauffman TL, Jarvik GP, et al. Lessons learned from a study of genomics-based carrier screening for reproductive decision making. Health Aff (Millwood). 2018 May; 37(5):809-816.


Medical Policy Group, December 2019 (9): New policy.

Medical Policy Administration Committee, January 2020.

Available for comment January 15 through March 1, 2020.

Medical Policy Group, January 2020 (9): Added CPT codes 81224, 81336, 81337 to current coding section.

Medical Policy Group, August 2020 (9): 2020 Update to Key Points. Added CPT code 81443 to current coding section. No new references added. No changes to policy statement.

Medical Policy Group, September 2021 (9): 2021 Update to Key Points and References. No changes to policy statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.