Germline BRCA1 and BRCA2 mutations are implicated in 25-50% of hereditary breast cancer cases. BRCA1 and BRCA2 are tumor suppressor genes that have an essential role in both DNA repair and cell cycle control systems. 


Germline BRCA1 and BRCA2 mutations are implicated in 25-50% of hereditary breast cancer cases. BRCA1 and BRCA2 are tumor suppressor genes that have an essential role in both DNA repair and cell cycle control systems. 

Disease Name 
Hereditary breast and ovarian cancer
Disease Information 

Hereditary breast and ovarian cancer (HBOC) is an autosomal dominant cancer predisposition syndrome caused by germline BRCA1/2 mutations. Mutations in these two highly penetrant genes increase the chance for cancer of the breast, ovaries and Fallopian tubes, pancreas and prostate.3,4 Studies suggest female BRCA1 mutation carriers have a 57-87% risk to develop breast cancer and a 39-40% risk to develop ovarian cancer by age 70.4-9 Similarly, male BRCA1 mutation carriers have a cumulative breast cancer risk of 1.2% by age 70.10,11

Similar studies suggest female BRCA2 mutation carriers have a 45-84% risk to develop breast cancer and an 11-18% risk to develop ovarian cancer (including primary peritoneal and Fallopian tube) by age 70.7-9,14 Male BRCA2 mutation carriers have up to a 15% prostate cancer risk and a cumulative breast cancer risk of 6.8% by ages 65 and 70, respectively.10-14 Furthermore, BRCA1/2 mutation carriers are at an increased risk for melanoma and cancer of the pancreas and possibly other cancers. Cancer risks are further modified by family history, reproductive choices, lifestyle and environmental factors, and other genetic factors.

BRCA1/2 mutations are more common in individuals of Ashkenazi Jewish (AJ) descent, with a carrier frequency of 1/40 or 2.6%,4,5 compared to a frequency of 0.2% or 1/500 in the non-AJ general population. Three founder mutations: BRCA1 gene c.68_69delAG (BIC: 185delAG) and c.5266dupC (BIC: 5382insC) and one in BRCA2 c.5946delT (BIC: 6174delT), account for up to 99% of identified AJ mutations.4,5 BRCA1 185delAG has a frequency of 1% and attributes to 16-20% of breast cancer cases diagnosed before 50 years of age; BRCA1 5382insC with a frequency of 0.13%. BRCA2 6174delT has a frequency of 1.52% in the AJ population and attributes to 15% of breast cancer cases diagnosed before 50 years of age.4,5

Testing Benefits & Indication 

Genetic testing is useful to:

  • Diagnose a personal and/or family history suggestive of hereditary breast and ovarian cancer  
  • Provide appropriate screening recommendations and risk-reducing options for BRCA1 or BRCA2 mutation-positive patients and their relatives

BRCA1/2 testing may be considered for individuals with a personal or family history of any of the following: 

  • Early-onset breast cancer (<45 years of age) or bilateral breast cancer
  • 2 primary breast cancers, or clustering of breast and ovarian cancer
  • Presence of male breast cancer
  •  Ovarian cancer at any age
  • At-risk populations (e.g. Ashkenazi Jewish descent)

The American Society of Clinical Oncology (ASCO) recommends that genetic testing be offered to individuals with suspected inherited (genetic) cancer risk in situations where test results can be interpreted and when they can affect medical management of the patient.2 If increased risk of a hereditary cancer syndrome is suspected, the American Congress (formerly College) of Obstetricians and Gynecologists (ACOG) recommends referral to a specialist in cancer genetics or a healthcare provider with expertise in genetics for complete hereditary cancer risk assessment, which may lead to genetic testing.16

Test Description 

BRCA1 coding exons 1-22, BRCA2 coding exons 1-26, and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for BRCA1 coding exons 1-22 and BRCA2 coding exons 1-26. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by incorporating the gDNA onto a microfluidics chip, along with primer pairs followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing, or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls are verified by Sanger sequencing. Gross deletion/duplication analysis of BRCA1 and BRCA2 using the multiplex ligation-dependent probe amplification (MLPA) kit is also performed.

Mutation Detection Rate 

Ambry's BRCA1/2 analysis can detect >99.9% of described mutations in both genes, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above in the Quick Links section at the top of this page.

Turnaround Time 
8838 BRCA1/2 Gene Sequence and 
Deletion/Duplication Analyses (Concurrent)                                          
(Blood)  6 - 10
(Saliva)  6 - 10
5892 BRCA Ashkenazi Jewish 3-site Mutation panel 6-10
5894 BRCA Ashkenazi Jewish 3-site Mutation panel 
with reflex to BRCA1/2 Analysis if negative
5890 BRCA1/2 Deletion/Duplication Analysis only 6-10
5864 BRCA1 Specific Site Analysis 7-14
5884 BRCA2 Specific Site Analysis 7-14


  1. National Comprehensive Cancer Network. Clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian. Available at: 2010. Accessed 5.29.13.
  2. American Society of Clinical Oncology Policy Statement Update: Genetic testing for cancer susceptibility. J Clin Oncol. 2003 Jun 15; 21(12):2397-406.
  3. Rohini R, et al. BRCA1 and BRCA2: different roles in a common pathway of genome protection. 2012. Nature.12:68-78.
  4. Ferla R, et al. Founder mutations in BRCA1 and BRCA2 genes. Annals of Oncology. 2007. 18;(Supplement 6):vi93-vi98.
  5. Janavivius R. Founder BRCA1/2 mutations in Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA Journal. 2010. 1:397-412.
  6. Tulinius H, et al. The effect of a single BRCA2 mutation on cancer in Iceland. J Med Genet. 2002. 39:457-462
  7. Ford D, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998. 62(3):676-689. 
  8. Antoniou A, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003. 72(5):1117-1130. 
  9. Chen S, et al. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007. 25(11):1329-1333. 
  10. Tai Y, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. 2007. J Natl Canc Inst99(23):1811-1814. 
  11. Thompson  D, et al. Cancer incidence in BRCA1 mutation carriers. J Natl Canc Inst. 2002. 94(18):1358-1365. 
  12. Kote-Jerai Z, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. British J Cancer. 2011. 105(8):1230-1234. 
  13. Folkins A and Longacre T. Hereditary gynecological malignancies: advances in screening and treatment. Histopathology. 2013. 62:2-30.
  14. Mahoney-Shannon K and Chittenden A. Genetic testing by cancer site: breast. The Can Journal. 2012. 18(4):310-319.
  15. Van Asperen C, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005. 42(9):711-719.
  16. American Congress of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 634: Hereditary cancer syndromes and risk assessment. Obstet Gynecol. June 2015. 125(6):1538-1543.