CurrentCapital BluecrossPolicy MP 2.377

Molecular testing for germline variants associated with ovarian cancer (BRIP1, RAD51C, RAD51D, NBN)

Defines medical necessity and investigational indications for germline testing of BRIP1, RAD51C, RAD51D, and NBN for ovarian cancer risk assessment in adults; applies to Capital BlueCross products as specified. Affects ordering providers and members being evaluated for hereditary ovarian cancer risk.

Policy Summary

PayerCapital Bluecross

PolicyMolecular testing for germline variants associated with ovarian cancer (BRIP1, RAD51C, RAD51D, NBN)

Policy CodePolicy MP 2.377

Change TypeNo material change

Effective Date1/1/2026

Next Review DateN/A

Key ActionObtain prior authorization when ordering germline testing for BRIP1, RAD51C, or RAD51D and document diagnosis, family relationships, and proband status.

SourceLink

Related Billing Codes

CPT-0103U-OVANEXT-25-GENE-HEREDITARY-OVARIAN-CANCER-PANEL

CPT 0103U: OvaNext® 25-Gene Hereditary Ovarian Cancer Panel

CPT-0475U-PROSTATE-GERMLINE-PANEL-PROSTATENOW

CPT 0475U: Prostate Germline Panel (ProstateNow™)

CPT-81432-HEREDITARY-BREAST-CANCER-GENE-PANEL-SEQUENCE-AND-CNV

CPT 81432: Hereditary Breast Cancer Multi-Gene Sequencing Panel

CPT-0134U-RNAINSIGHT-CANCERNEXT-MRNA-SEQUENCE-ANALYSIS-18-GENE-PANEL

CPT 0134U: +RNAinsight™ for CancerNext® 18-Gene mRNA Panel

CPT-81479-UNLISTED-MOLECULAR-PATHOLOGY-PROCEDURE

CPT 81479: Unlisted Molecular Pathology Procedure

CPT-0102U-BREASTNEXT-GENOMIC-SEQUENCE-ANALYSIS-17-GENE-PANEL

CPT 0102U: BreastNext® 17-Gene Hereditary Breast Cancer Panel

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

3genes medically necessary when criteria met

1gene investigational for ovarian cancer risk

70%late-stage diagnoses (%)

20%+estimated hereditary proportion

7references cited

Coverage Criteria

Medically necessary indications (BRIP1, RAD51C, RAD51D)

Covered when ALL of the following are met for BRIP1, RAD51C, and RAD51D germline testing in adults:

Primary coverage criteria: The individual has a diagnosis of epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; AND the individual has not previously been tested for these gene variants; AND the individual is thought to be the most informative member of a family (proband) to have genetic testing; AND the individual has closely related (first- and/or second-degree) relatives who are considering genetic testing for these gene variants to inform prophylactic decision-making or who have test results that cannot be fully interpreted without testing an affected relative.

Support: [[1],[3]]

Alternate covered scenario: The individual has not been diagnosed with epithelial ovarian cancer; AND the individual has any blood relative with a known pathogenic/likely pathogenic BRIP1, RAD51C, or RAD51D variant; OR the individual has a first- or second-degree relative diagnosed with ovarian cancer.

Support: [[1]]

Coverage for BRIP1, RAD51C, RAD51D germline testing

Covered when ALL of the following are met for asymptomatic individuals/families considering risk-reducing interventions or testing an affected relative:

Primary criteria: Testing for BRIP1, RAD51C, or RAD51D is supported to provide more precise risk estimates in women without diagnosed epithelial ovarian cancer but in families at risk of developing epithelial ovarian cancer, and when results would inform consideration of risk-reducing interventions (for example, risk-reducing salpingo-oophorectomy).

Evidence sufficient to improve net health outcome

Relative testing: Genetic testing of first- and/or second-degree relative(s) with personal history of epithelial ovarian cancer to identify a familial BRIP1, RAD51C, or RAD51D variant is supported to guide prophylactic decision-making in undiagnosed at-risk members; testing of relatives with early-onset, bilateral, or multiple primaries is recommended to maximize informative results.

Supported by indirect evidence from risk-reducing intervention studies

Insufficient evidence / Not covered indications

Not covered / insufficient evidence when the following apply:

NBN testing in asymptomatic at-risk individuals: Germline testing of NBN for individuals without diagnosed epithelial ovarian cancer in families at risk is considered investigational due to insufficient evidence to determine improvement in net health outcome; national guidelines have not recommended risk-reducing interventions for NBN carriers because penetrance and absolute risk are not established.

Insufficient evidence for recommendation

Use to guide therapy in diagnosed OC: Germline testing of BRIP1, RAD51C, RAD51D, and NBN in individuals with diagnosed ovarian cancer to guide treatment decisions (maintenance or recurrence therapy) is considered investigational because current evidence does not demonstrate clinically actionable results to improve net health outcomes outside clinical trials.

Evidence lacking for actionable treatment decisions

Evidence base and guideline citations

Supporting evidence and guideline references informing coverage decisions

Guideline and evidence support: Coverage informed by NCCN and ASCO guidelines and multiple genetic association and penetrance studies identifying BRIP1, RAD51C, and RAD51D as associated with increased ovarian cancer risk; NBN is noted as having inconsistent evidence and was designated investigational in prior policy updates.

References include NCCN Genetic/Familial High-Risk Assessment (v3.2024), NCCN Ovarian Cancer (v2.2024), ASCO guidance, and multiple J Clin Oncol/J Natl Cancer Inst studies

Testing for germline NBN variants for ovarian cancer risk assessment in adults is designated investigational and excluded from coverage because there is insufficient evidence to conclude that testing improves health outcomes or should inform clinical management for at-risk, asymptomatic individuals.

When a family member is diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline testing of BRIP1, RAD51C, or RAD51D may be performed on that affected relative (the proband) to identify a familial pathogenic/likely pathogenic variant that could then be used for targeted testing in other at-risk relatives; this testing approach is supported when results would influence prophylactic decision-making.

NBN testing is excluded because studies report inconsistent mutation frequency, uncertain penetrance estimates, and national guidelines have not recommended risk-reducing interventions for NBN carriers; therefore evidence is insufficient to support clinical utility for informing prophylactic surgery or other interventions.

Per policy history, NBN was added as investigational in the 12/30/2022 minor review; tests designated investigational are not covered for routine clinical management.

Germline testing of BRIP1, RAD51C, and RAD51D when performed outside the defined coverage criteria (for example, without an informative family history or unrelated to prophylactic decision-making) is considered investigational and not medically necessary.

Germline testing of BRIP1, RAD51C, RAD51D, and NBN in individuals already diagnosed with ovarian cancer does not currently provide clinically actionable information to guide therapy or maintenance/recurrence treatment outside of clinical trials and is considered to have insufficient evidence for that purpose.

The policy previously noted testing to guide treatment for a diagnosed individual as investigational; that designation remains in place and such use may be denied due to lack of demonstrated clinical benefit.

Covered Indications

BRIP1, RAD51C, RAD51D germline testing for ovarian cancer risk assessment in adults who meet the policy criteria

BRIP1, RAD51C, RAD51D germline testing for ovarian cancer risk assessment is covered in adults who meet policy criteria when performed to inform familial risk assessment or prophylactic decisions.

Covered scenario A: Testing an affected (diagnosed) proband (epithelial ovarian, fallopian tube, or primary peritoneal cancer) who is the most informative family member, when at least one first- or second-degree relative is considering genetic testing or has results that require interpretation.

See required documentation and recommended testing sequence

Covered scenario B: Testing an unaffected individual when there is a known familial pathogenic/likely pathogenic BRIP1, RAD51C, or RAD51D variant in any blood relative, or when the individual has a first- or second-degree relative diagnosed with ovarian cancer, and results would influence consideration of risk-reducing interventions.

Targeted familial variant testing is preferred when the familial variant is known

Unexplained family history suggestive of hereditary ovarian cancer or testing a relative with EOC

Eligibility Requirements

Coverage requires that the individual tested be linked to closely related family members (first- and/or second-degree relatives) who are considering testing or risk-reducing interventions, or that a known familial pathogenic/likely pathogenic variant exists; family history and pedigree information should support that testing would inform prophylactic decision-making.

For unaffected individuals, coverage is contingent on a blood relative having a known pathogenic/likely pathogenic BRIP1, RAD51C, or RAD51D variant or on having a first- or second-degree relative with ovarian cancer such that testing would meaningfully inform risk and management.

When a familial pathogenic/likely pathogenic variant is already identified, targeted testing for that specific variant in at-risk relatives is recommended and preferred over broad sequencing, as it provides a more precise risk estimate and reduces uninformative or non-actionable results.

Not Covered / Investigational

Germline NBN testing is investigational and not covered. In addition, testing of BRIP1, RAD51C, RAD51D, and NBN that does not meet the policy’s coverage criteria (including testing intended to guide treatment of a diagnosed individual or testing in asymptomatic individuals without relevant family history) is not covered due to insufficient evidence of clinical utility.

Restating the policy stance: NBN testing for ovarian cancer risk assessment is investigational and excluded from coverage; similarly, use of germline results to guide therapy in patients with diagnosed ovarian cancer lacks sufficient evidence and is not covered outside clinical trials.

Evidence summaries indicate that while BRIP1, RAD51C, and RAD51D testing can inform prophylactic decisions in at-risk families, NBN has inconsistent data on mutation frequency and penetrance and therefore is not supported for clinical decision-making in asymptomatic individuals.

Testing NBN in asymptomatic at-risk individuals and using BRIP1/RAD51C/RAD51D/NBN results to guide treatment in diagnosed ovarian cancer patients are explicitly identified as lacking sufficient evidence for clinical utility and are not covered.

The 12/30/2022 minor review added the investigational designation for NBN; that administrative update is reflected in the policy history and supports the current not-covered status for NBN testing.

Coding

Investigational when used for testing BRIP1, RAD51C, and RAD51D variantsCPTNot Covered

0102U
0103U
0134U
81432

Covered when medically necessary when used for testing BRIP1, RAD51C, and RAD51D variantsCPTCovered

81479

Associated ICD-10 diagnosis codes referencedICD-10

C48.0	Malignant neoplasm of retroperitoneum.
C48.1	Malignant neoplasm of specified parts of peritoneum.
C48.2	Malignant neoplasm of peritoneum, unspecified.
C48.8	Malignant neoplasm of overlapping sites of retroperitoneum.
C56.1	Malignant neoplasm of right ovary.
C56.2	Malignant neoplasm of left ovary.
C56.3	Malignant neoplasm of bilateral ovaries.
C56.9	Malignant neoplasm of unspecified ovary.
C57.00	Malignant neoplasm of unspecified fallopian tube.
C57.01	Malignant neoplasm of right fallopian tube.

1–10 of 17

1/2

Administrative coding changesCPT | HCPCS

0475U	Added code (molecular test code) per administrative update
0131U	Previously listed code removed effective 01/01/2026
0132U	Previously listed code removed effective 01/01/2026
0135U	Previously listed code removed effective 01/01/2026

ICD-10 additionsICD-10

Z85.4A	ICD-10 code added (effective 10/01/2025) per administrative update
Z86.00A	ICD-10 code added (effective 10/01/2025) per administrative update

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for germline BRIP1, RAD51C, and RAD51D testing when performed for ovarian cancer risk assessment. Providers should obtain prior authorization before ordering these tests to confirm medical necessity under the policy.

Prior authorization applies to sequence- and panel-based testing for BRIP1, RAD51C, and RAD51D when used for hereditary ovarian cancer risk assessment.

Billing Rule

Code-based Prior Authorization Note

Some procedure codes listed in the coding section are designated investigational or covered only when medically necessary. Use the coding section as a guide but verify coverage and prior authorization requirements with payer systems.

Background

Epithelial ovarian cancer (including fallopian tube and primary peritoneal carcinomas) comprises the majority of ovarian cancers and often presents at an advanced stage with poor survival. Hereditary predisposition accounts for over 20% of cases, with BRCA1/2 explaining a large proportion and additional moderate-penetrance genes such as BRIP1, RAD51C, and RAD51D contributing to inherited risk; identifying high-risk individuals can inform consideration of risk-reducing interventions.

Definitions

Degree of relatives — definitions

First-degree relativesParents, siblings, and children.

Second-degree relativesGrandparents, aunts, uncles, nieces, nephews, grandchildren, and half-siblings.

Use in coverage criteriaPolicy uses first- and second-degree relative definitions to determine eligibility for testing when relatives are considering risk-reducing interventions or when a familial pathogenic variant is known.

Variant classification terminology (ACMG-AMP)

ACMG-AMP standard termsPathogenic; Likely pathogenic; Variant of uncertain significance; Likely benign; Benign.

Nomenclature guidanceHGVS nomenclature is used for reporting variants in clinical testing as an international standard.

Provider Resources & Counseling

Documentation Required

Formal genetic counseling recommended

Formal genetic counseling is recommended when genetic testing for inherited conditions is considered and should be performed by someone experienced in genetic medicine and testing methods.

Documentation Required

Perform testing within counseling and risk-assessment context

Genetic testing should be performed in the context of counseling and risk assessment; identification of pathogenic variants informs discussions about benefits and harms of interventions such as RRSO or chemoprevention.

Note

Guidelines imply counseling; explicit requirement not stated

Although guideline citations imply the role of genetic counseling, the policy excerpts do not state an explicit pre- or post-test counseling requirement as a condition of coverage.

Revision History

2025-12-04administrative

Removed CPT/HCPCS codes 0131U, 0132U, and 0135U effective 01/01/2026.

2025-09-03administrative

Added ICD-10 codes Z85.4A and Z86.00A effective 10/01/2025.

2025-06-25administrative

Removed Benefit Variations section and updated Disclaimer.

Policy Summary

PayerCapital Bluecross

PolicyMolecular testing for germline variants associated with ovarian cancer (BRIP1, RAD51C, RAD51D, NBN)

Policy CodePolicy MP 2.377

Change TypeNo material change

Effective Date1/1/2026

Next Review DateN/A

Key ActionObtain prior authorization when ordering germline testing for BRIP1, RAD51C, or RAD51D and document diagnosis, family relationships, and proband status.

SourceLink

On This Page

Testing a relative with epithelial ovarian cancer is supported when results would influence prophylactic decisions for at-risk family members:

Relative selection: Preferentially test a first- or second-degree relative with personal history of epithelial ovarian cancer, especially individuals with early-onset disease, bilateral disease, or multiple primaries, because they have the highest likelihood of yielding an informative, positive test result.

Supports targeted testing to identify familial variant

Impact on management: Identification of a familial BRIP1, RAD51C, or RAD51D pathogenic/likely pathogenic variant in a relative provides more precise risk estimates for unaffected family members and can inform consideration of risk-reducing salpingo-oophorectomy or other interventions.

Evidence is indirect but sufficient to improve net health outcome in risk-reduction context

Evaluation of inherited susceptibility to ovarian cancer via germline testing for BRIP1, RAD51C, RAD51D (evidence-supported)

Germline testing for BRIP1, RAD51C, and RAD51D is supported as part of evaluation for inherited susceptibility to ovarian cancer when evidence-based criteria are met:

Evidence-supported use: Testing is appropriate to evaluate inherited susceptibility to ovarian cancer in individuals and families meeting the policy criteria because multiple studies and clinical guidelines demonstrate these genes confer moderate-penetrance risks and that identifying carriers can inform risk estimation and management.

References: multiple genetic association studies and NCCN/ASCO guidance

Investigational/covered code lists may change — confirmation via prior auth portals or billing resources is recommended.

Codes 0102U, 0103U, 0134U, and 81432 are listed as investigational when used for testing BRIP1, RAD51C, and RAD51D variants (see Coding Information).

Code 81479 and certain CPT/ICD-10 codes are listed under covered when medically necessary; check member benefits for reimbursement eligibility.

Documentation Required

Coding Verification Required

Providers must verify that the procedure and diagnosis codes submitted on claims match the testing ordered and the clinical indication. Coding errors or use of investigational codes for covered situations may result in claim denial.

Confirm CPT/HCPCS and ICD-10 codes before submission.
Ensure use of current code sets — codes are subject to change and the policy coding table may not be exhaustive.
Examples of relevant codes appear in the policy coding section; confirm status (investigational vs covered) prior to billing.

Denial Risk

NBN Germline Testing — Investigational

Testing for germline NBN variants for ovarian cancer risk assessment is considered investigational. Orders for NBN germline testing for this indication may be denied and require documentation of clinical justification; prior authorization will not convert investigational indications to covered indications.

NBN germline testing is investigational due to insufficient evidence of clinical validity and utility for ovarian cancer risk assessment.
Testing of NBN to guide prophylactic surgery decisions is not supported by established guideline recommendations and is considered investigational.

Note

Policy History / Administrative Updates

Policy history: this policy was originally adopted as a new policy (effective 05/01/2021) and has undergone multiple administrative and clinical updates, including addition of NBN investigational statement, coding updates, temporary retirement/combination with MP 2.211, and subsequent reinstatement and administrative code changes.

Effective 05/01/2021 — New Policy adopting BCBSA policy with medically necessary criteria for BRIP1, RAD51C, RAD51D.
12/30/2022 — Minor Review: Added NBN investigational statement and title change; updated coding and references.
12/22/2023 — Retirement Review: Policy combined with MP 2.211.
06/07/2024 — Administrative Update: Added 0475U.
01/14/2025 — Minor Review: Policy brought out of retirement.
06/25/2025 — Administrative Update: Removed Benefit Variations Section; updated Disclaimer.
09/03/2025 — Administrative Update: Added ICD10 Codes Z85.4A & Z86.00A eff 10/01/2025.
12/04/2025 — Administrative Update: Removed codes 0131U, 0132U & 0135U eff 01/01/2026.

Documentation Required

Recommended Testing Sequence (Test Affected Family Member First)

Recommended testing sequence: test the most informative (affected) family member first. If a pathogenic/likely pathogenic familial variant is identified in an affected relative, perform targeted testing for that specific variant in at-risk, unaffected relatives rather than full gene sequencing. If no affected relative is available, counsel regarding limitations of testing in unaffected individuals (uninformative negative results, higher prevalence of VUS).

When a known familial BRIP1, RAD51C, or RAD51D variant exists, perform targeted testing for that variant in relatives.
When the familial variant is unknown, prioritize testing an affected relative with early-onset, bilateral, or multiple primary disease (the proband).
If an affected relative is unavailable or declines testing, testing an unaffected at-risk relative may be considered after counseling about limitations and potential for VUS or uninformative negative results.

Documentation Required

Required Clinical Documentation — Diagnosis and Family Relationships

Ordering clinicians must document the clinical indication, relevant diagnosis, and degree of family relationship (proband status and relationship to other relatives) in the medical record and as part of prior authorization. Documentation should include pedigree, validated risk model results, or a family history consistent with hereditary ovarian cancer when relevant to the request.

Record the proband status (most informative affected family member) when applicable.
Provide a multigenerational pedigree or summary of family history, or results from validated risk models (e.g., BRCAPRO, BOADICEA/CanRisk) when available.
Document whether testing is for prophylactic surgery decision-making, diagnostic evaluation, or treatment guidance; note that testing to guide treatment in diagnosed individuals for these genes is considered investigational.

Source organizationsTerminology and interpretation guidance referenced from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP).

RAD51C / RAD51D — gene description

Gene family/functionRAD51C and RAD51D are RAD51 paralogs involved in the BRCA1/2 homologous recombination DNA repair pathway.

Cancer risk associationPathogenic germline variants in RAD51C and RAD51D are associated with increased ovarian cancer risk; evidence from multiple studies supports their contribution to inherited ovarian cancer susceptibility.

Biallelic effectsBiallelic missense mutations in RAD51C are associated with a Fanconi anemia–like phenotype in rare cases.

NBN — gene description

Protein encodedNBN encodes nibrin (p95), a member of the MRE11–RAD50 double-strand break repair complex.

Cellular roleImplicated in double-strand break repair, cell cycle checkpoint functions, and cellular responses to ionizing radiation.

Association with ovarian cancerAssociation with ovarian cancer risk is inconsistent and penetrance is not well established; policy treats NBN germline testing for ovarian cancer risk assessment as investigational.

Germline molecular testing — definition

DefinitionGermline molecular testing is sequence analysis and variant interpretation performed to identify inherited pathogenic or likely pathogenic variants in genes associated with ovarian cancer susceptibility (e.g., BRIP1, RAD51C, RAD51D, NBN).

Test types referencedIncludes single‑gene testing, targeted familial variant testing, and multi‑gene NGS panels validated in clinical laboratories (laboratory‑developed tests under CLIA).

Interpretation standardsVariant interpretation and reporting should follow ACMG/AMP standards and use HGVS nomenclature for variant descriptions.

Documentation Required

Ordering clinicians must be able to document required information

Ordering is implicitly expected to be by clinicians who can document the required information (diagnosis, family history, proband status) to support medical necessity for testing.

Documentation supporting eligibility (diagnosis, pedigree, proband identification, known familial variant) should accompany authorization/claims.

2025-01-14minor_review

Brought the policy out of retirement.

2024-06-07administrative

Added HCPCS/CPT code 0475U effective 07/01/2024.

2023-12-22retirement_review

Policy combined with MP 2.211 (retirement review).

2022-12-30minor_review

Added NBN investigational statement and updated title, cross-references, background, rationale, coding table, and references.

2021-11-19minor_review

Updated criteria per BCBSA to allow individuals with a diagnosis of epithelial ovarian and related cancers; clarified testing to guide treatment is investigational and added NCCN statement, updated guidelines, FEP, background, CPT and ICD-10 codes.

2021-05-01policy_effectiveLatest

New policy effective adopting BCBSA policy with medically necessary criteria for BRIP1, RAD51C, and RAD51D variants.