BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer Syndrome

  • Germline analysis of the BRCA1 and BRCA2 genes in individuals with a suspected diagnosis of HBOC syndrome
  • When a relative has a previously identified pathogenic sequence variant, see Familial Mutation, Targeted Sequencing (2001961)
  • Recommended test for a known familial sequence variant previously identified in a family member
  • A copy of the family member’s test result documenting the familial variant is REQUIRED
  • Use to assess for large deletion/duplication previously identified in a family member
  • A copy of a relative’s lab report is REQUIRED

Pathogenic variants in the BRCA1 and BRCA2 genes are associated with hereditary breast and ovarian cancer (HBOC) syndrome. BRCA1- and BRCA2-associated HBOC syndrome is often characterized by early age of cancer onset (typically before 50 years of age) and multiple, multifocal, and/or similar cancers in a single individual or in a closely related family member(s). Individuals with a single germline BRCA1 or BRCA2 pathogenic variant have an increased risk for breast (female and male), ovarian, fallopian tube, peritoneal, pancreatic, prostate, melanoma, and other cancers. Analysis of the BRCA1 and BRCA2 genes is offered through ARUP's BRCA1 and BRCA2-Associated HBOC Syndrome Panel. For a more comprehensive test for hereditary causes of breast and/or ovarian cancer, please see the Hereditary Breast and Ovarian Cancer Panel, which includes analysis of several genes, including BRCA1 and BRCA2.

Disease Overview

Associated Disorder

BRCA1- and BRCA2-associated HBOC syndrome

  • Caused by a single germline BRCA1 or BRCA2 pathogenic variant 
  • Individuals are at increased risk for the following cancers (combined estimated risks for BRCA1 and BRCA2 listed below) :
    • Breast (female): 38-87%
    • Breast (male): 1.2-8.9%
    • Ovarian (including fallopian tube and peritoneal): 16.5-63%
    • Pancreatic: 1-7%
    • Prostate: 8.6-20%
    • Melanoma: elevated for BRCA2 only


At least 5-10% of all breast cancers and 10-15% of all ovarian cancers are associated with a hereditary cause.   


One in 400 individuals from the general population or 1 in 40 Ashkenazi Jewish individuals have a BRCA1 or BRCA2 pathogenic variant.  


  • Single pathogenic variants in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant manner and are associated with HBOC syndrome.
  • BRCA1 and BRCA2 pathogenic variants are also associated with autosomal recessive Fanconi anemia.

Test Description

Genes Tested

  • BRCA1 (NM_007294) and BRCA2 (NM_000059)
  • See Genes Tested table for more information.

Clinical Sensitivity

BRCA1 and BRCA2 sequencing and deletion/duplication testing detects 20-60% of hereditary breast and/or ovarian cancers, in general.   

  • >80% of BRCA1 and BRCA2 variants are detectable by sequencing.
  • ~10% of BRCA1 and BRCA2 variants are detectable by large deletion/duplication analysis.

Testing Strategy

Contraindications for Ordering

  • Should not be ordered to detect somatic variants associated with malignancy because sensitivity for mosaic variants is low with methodology used for germline assays
  • Individuals with hematologic malignancy and/or a previous allogeneic bone marrow transplantation should not undergo molecular genetic testing on a peripheral blood specimen.
    • Testing of cultured fibroblasts is required for accurate interpretation of test results.
  • When a relative has a previously identified pathogenic variant, see Familial Mutation, Targeted Sequencing.


  • A negative result does not exclude a heritable form of cancer.
  • Diagnostic errors can occur due to rare sequence variations.
  • Interpretation of this test result may be impacted if this individual has had an allogeneic stem cell transplantation.
  • The following will not be evaluated:
    • Variants outside the coding regions and intron-exon boundaries of the targeted genes
    • Regulatory region variants and deep intronic variants
    • Breakpoints of large deletions/duplications
  • The following may not be detected:
    • Deletions/duplications/insertions of any size by massively parallel sequencing
    • Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions
    • Low-level somatic variants

Analytical Sensitivity

  • Analytical sensitivity for multiplex ligation-dependent probe amplification (MLPA) is 99%.
    • Approximately 99% for single nucleotide variants (SNVs) and >93% for insertions/duplications/deletions from 1-10 base pairs in size
    • Variants >10 base pairs may be detected, but analytical sensitivity may be reduced.

Genes Tested

Gene MIM Number Disorder Inheritance



HBOC syndrome

Associated cancer(s)/tumor(s): breast, ovarian, fallopian tube, peritoneal, pancreatic, prostate


Fanconi anemia, complementation group S




HBOC syndrome

Associated cancer(s)/tumor(s): breast, ovarian, fallopian tube, peritoneal, pancreatic, prostate, melanoma


Fanconi anemia, complementation group D1


AD, autosomal dominant; AR, autosomal recessive


Additional Resources