# Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT)

Source: https://onco.cc/terms/founder-mutation/  
OnCo record `founder-mutation` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A founder mutation is a single inherited gene fault that many people in one population share because they descend from the same ancestor who carried it. The best known are three BRCA faults carried by about one in forty Ashkenazi Jews, which is why Jewish ancestry is one of the family history flags in UK genetics referral rules.

## Summary

In a population study of about 3,000 Ashkenazi Jewish individuals unselected for breast cancer, the BRCA1 185delAG mutation had a carrier frequency of 1.09 percent and 5382insC 0.13 percent, and in 3,085 individuals the BRCA2 6174delT mutation 1.52 percent, confirming 185delAG and 6174delT as the two most frequent alleles predisposing to hereditary breast cancer among the Ashkenazim and suggesting lower penetrance for 6174delT (Roa 1996). Among 5,318 Jewish volunteers in Washington, 120 carriers of one of the three mutations were identified; by age 70 the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval 40 to 73), of ovarian cancer 16 percent and of prostate cancer 16 percent, with no difference between BRCA1 and BRCA2 carriers and risks well below the 85 percent estimated from high-risk families (Struewing 1997). Because the combined frequency exceeds 2 percent, testing for the three variants is informative in this population without a family history, and NICE CG164 lists Jewish ancestry among the features for which clinicians should seek advice from a specialist genetics service and asks clinics to record ethnic background when assessing carrier probability; Cancer Research UK's family history page names a Jewish background as a reason the clinic may consider testing more likely to be useful. BRCA1 founder mutations matter for triple-negative disease because BRCA1-associated cancers are mostly basal-like and triple-negative (Atchley 2008). Other populations have their own founder alleles; the history on the parent page records the Polish BRCA1 variants beside the Ashkenazi ones.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: Founder variant; Ashkenazi BRCA founder mutations; BRCA1 185delAG; BRCA1 5382insC; BRCA2 6174delT; Population-specific BRCA mutation
- Tags: breast; tnbc

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Founder_effect
- Roa, Nat Genet 1996: Ashkenazi Jewish population frequencies for the common BRCA1 and BRCA2 mutations: https://doi.org/10.1038/ng1096-185
- Struewing, N Engl J Med 1997: cancer risk with the BRCA1 and BRCA2 founder mutations among Ashkenazi Jews (5,318 volunteers): https://doi.org/10.1056/nejm199705153362001
- NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention): https://www.nice.org.uk/guidance/cg164/chapter/Recommendations
- CRUK: family history and inherited genes in breast cancer: https://www.cancerresearchuk.org/about-cancer/breast-cancer/risks-causes/family-history-and-inherited-genes
- Atchley, J Clin Oncol 2008: clinical and pathological characteristics of BRCA-positive and BRCA-negative breast cancer: https://doi.org/10.1200/jco.2008.16.6231

## Connected records

- cancers: [BRCA-associated triple-negative breast cancer](https://onco.cc/cancers/brca-associated-tnbc/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- terms: [Germline BRCA testing criteria for triple-negative breast cancer (UK)](https://onco.cc/terms/germline-brca-testing-criteria-tnbc/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/)

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