U.S. flag

An official website of the United States government

GTR Home > Tests > BRCA2-Hereditary Cancer of the Breast


Test order codeHelp: Breast Cancer (BRCA1/BRCA2)

Test name


BRCA2-Hereditary Cancer of the Breast (HBOC-BRCA2)

Purpose of the test


This is a clinical test intended for Help: Diagnosis, Mutation Confirmation, Pre-symptomatic, Predictive, Prognostic, Recurrence, Risk Assessment



Loading data ......

Click Indication tab for more information.

How to order


Please complete the requisition available on the website and ensure it is signed by the referring physician. Referrals only accepted through a cancer genetics clinic
Order URL Help: http://www.lhsc.on.ca/palm/molecular/panels.html#cancer

Specimen source

Isolated DNA
Paraffin block
Peripheral (whole) blood


Molecular Genetics
DDeletion/duplication analysis
Multiplex Ligation-dependent Probe Amplification (MLPA)
  • Applied Biosystems 3730 capillary sequencing instrument
Next-Generation (NGS)/Massively parallel sequencing (MPS)
  • Illumina MiSeq/NextSeq
CSequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
  • Applied Biosystems 3730 capillary sequencing instrument
  • Illumina MiSeq/NextSeq

Summary of what is tested

Loading data ......

Click Methodology tab for more information.

Clinical utility


Establish or confirm diagnosis

Guidance for management

Avoidance of invasive testing

Predictive risk information for patient and/or family members

Clinical validity


A germline mutation in BRCA1 or BRCA2 predisposes to breast and ovarian cancer as well as other cancers. The risk of developing cancer that is associated with a germline BRCA1 or BRCA2 mutation, which has been derived from families with multiple affected individuals, families with few affected individuals, and from population-based studies, appears to be variable within families. Prognosis for breast and ovarian cancer depends on the stage at which the cancer is diagnosed; however, studies on survival have revealed conflicting results for individuals with germline BRCA1 or BRCA2 mutations when compared to controls.


Testing strategy


All coding exons and 20 bp of flanking non-coding sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >300x mean read depth coverage, with a minimum 100x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. Variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868), if necessary, are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. Variants detected in the 5’ UTR and 3’ UTR are not reported unless there is evidence suggesting pathogenicity. This assay has been validated at a level of sensitivity equivalent to the Sanger sequencing and standard copy number analysis (>99%; PMID: 27376475,28818680). 000 Please complete the requisition available on the website and ensure it is signed by the referring physician. Referrals only accepted through a cancer genetics clinic

Test services

  • Clinical Testing/Confirmation of Mutations Identified Previously
  • Confirmation of research findings
  • Custom Deletion/Duplication Testing
  • Custom Sequence Analysis
  • Custom Prenatal Testing
  • Custom mutation-specific/Carrier testing

Suggested reading

  • USPSTF, 2019
    Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force
  • USPSTF, 2013
    Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation (See 2019 Update)
  • Phillips et al., 2013
    Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
  • Domchek et al., 2010
    Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality

Practice guidelines

  • NICE, 2023
    UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023
  • NCCN, 2022
    NCCN Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic version 2.2022
  • ACMG ACT, 2019
    American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.