rs80359351

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This is a frameshift variant variant in the BRCA2 gene.

Key Literature Trait Associations

Breast and Ovarian Cancer Risk

rs80359351 (BRCA2 6174delT) is a pathogenic frameshift variant and one of the three Ashkenazi Jewish BRCA founder mutations (~1% carrier frequency in Ashkenazi Jewish individuals). Carriers face a cumulative breast cancer risk of approximately 39% by age 70, which, while lower than other BRCA2 pathogenic variants (~61%), remains substantially elevated above the population baseline. Ovarian/fallopian tube cancer risk is estimated at ~16–21% lifetime penetrance. A landmark 1997 NEJM population-based study in 5,318 Jewish subjects estimated 56% breast cancer risk and 16% ovarian cancer risk by age 70 across BRCA1/2 founder mutations combined. ClinVar lists this variant as pathogenic across all 12 independent submissions.

Finch A et al. “The risks of breast and ovarian cancer associated with the Ashkenazi Jewish founder allele BRCA2 6174delT.” Clinical Genetics (2022)

Allele DELACAA

OR —

p 3.0e-3

N 967

Preliminary work

Ashkenazi Jewish

Struewing JP et al. “The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.” The New England Journal of Medicine (1997)

Allele DELACAA

OR —

p —

N 5,318

Preliminary work

Ashkenazi Jewish

Satagopan JM et al. “Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.” Clinical Cancer Research : an Official Journal of the American Association for Cancer Research (2002)

Allele DELACAA

OR —

p —

N 3,816

Preliminary work

Ashkenazi Jewish

Oddoux C et al. “The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%.” Nature Genetics (1996)

Allele DELACAA

OR 9.30

p —

N 1,255

Preliminary work

Ashkenazi Jewish

Neuhausen S et al. “Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.” Nature Genetics (1996)

Allele DELACAA

OR —

p 5.0e-3

N 173

Candidate gene study

Ashkenazi Jewish

Antoniou AC et al. “Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.” Journal of Medical Genetics (2005)

Allele DELACAA

OR —

p —

Candidate gene study

multi-ancestry

Gene information from NCBI Gene. Variant classifications from ClinVar.

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