rs80357713

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This is a frameshift variant variant in the BRCA1 gene.

Key Literature Trait Associations

Breast and Ovarian Cancer Risk

Carriers of this BRCA2 pathogenic frameshift variant face dramatically elevated lifetime risks: cumulative breast cancer risk to age 80 is approximately 69% (95% CI 61–77%) compared to ~12% in the general population, and cumulative ovarian cancer risk is approximately 17% (95% CI 11–25%). These estimates derive from a large prospective cohort of 3,820 BRCA2 carriers (Kuchenbaecker et al., JAMA 2017). The variant (c.1813dup, p.Ile605fs) has been detected in hereditary breast and ovarian cancer families across European, Algerian, and other populations, and was classified Pathogenic by the ENIGMA expert panel. A 113,927-participant study (Dorling et al., NEJM 2021) confirmed BRCA2 protein-truncating variants as among the highest-risk genes for breast cancer.

Kuchenbaecker KB et al. “Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.” Jama (2017)

Allele A

OR —

p —

N 3,820

Preliminary work

multi-ancestry

Dorling L et al. “Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.” The New England Journal of Medicine (2021)

Allele A

OR —

p 1.0e-100

N 113,927

Large GWAS

multi-ancestry

Rebbeck TR et al. “Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.” Human Mutation (2018)

Allele A

OR —

p —

N 29,700

Preliminary work

multi-ancestry

Mehemmai C et al. “BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report.” Pathology Oncology Research : Por (2020)

Allele A

OR —

p —

N 1,162

Preliminary work

North African (Algerian)

Hoyer J et al. “Addition of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria.” Bmc Cancer (2018)

Allele A

OR —

p —

N 229

Candidate gene study

European (German)

Prostate cancer

BRCA2 pathogenic truncating variants, including frameshift mutations like rs80357713 (c.1813dup), confer an approximately 8.6-fold increased risk of prostate cancer by age 65, with an absolute risk of ~15% by age 65. This risk is most pronounced for early-onset prostate cancer. A case report (PMID 34048828) identified BRCA2 c.1813dup (p.I605Nfs*11) specifically in a patient with metastatic prostate cancer, representing the first report of this variant in that disease context. Clinical guidelines now recommend BRCA2 testing as part of prostate cancer workup.

Kote-Jarai Z et al. “BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.” British Journal of Cancer (2011)

Allele A

OR 8.60

p —

N 1,864

Preliminary work

European (UK)

King MC et al. “Novel Case of Isolated Peritoneal Carcinomatosis from Metastatic Prostate Cancer Carrying a Pathogenic BRCA Mutation Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.” Urology (2021)

Allele A

OR —

p —

N 1

Candidate gene study

European

Gene information from NCBI Gene. Variant classifications from ClinVar.

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