biostudies-literatureChong ALResearch Institute of the McGill University Health CentreMerck CanadaInstitut de recherche, Centre universitaire de santé McGillMinistère de l'Économie, de l'Innovation et de l'Énergie du QuébecRéseau de recherche sur le cancer (RRCancer)Canadian Institutes of Health ResearchMerck Canada Inc.FRQS Cancer DivisionCIHR747-751https://www.ebi.ac.uk/biostudies/studies/S-EPMC12580481biostudies-literatureUnknown108(6)We identified a PMS2 variant (NM_000535.7:c.2117del, p.Lys706Serfs*19) in 22 French-Canadian (FC) families from Quebec with Lynch syndrome (LS; n = 21) or constitutional mismatch repair deficiency (CMMRD; n = 1). We aimed to (a) confirm its founder origin, (b) assess its allele frequency in the FC population, and (c) determine its contribution to the risk of developing various cancers in this population. We identified a haplotype common to all c.2117del alleles spanning 666 kb to 1.37 Mb, confirming the founder nature of the variant. In affected cases, the variant was found in 0 out of 821 breast cancer cases, 8 out of 693 (1.15%) endometrial cancer (EC) cases, and 1 out of 191 (0.52%) colorectal cancer (CRC) cases. In unaffected persons, the variant was identified in 22/6347 newborns (0.3Clinical geneticsPMS2 c.2117del (p.Lys706Serfs*19) is the Most Frequent Cancer-Associated Founder Pathogenic Variant in the French-Canadian Population of Quebec, Canada.PMC12580481FDN-148390FDN‐148390Mes-Masson AMChong GBehl SRousseau FCastonguay LGiroux SEl Haffaf ZDesilets VLevesque SFoulkes WDGravel SChong ALMaranda BMejia-Garcia AChenier SHamel NfalsePMS2 c.2117del (p.Lys706Serfs*19) is the Most Frequent Cancer-Associated Founder Pathogenic Variant in the French-Canadian Population of Quebec, Canada.We identified a PMS2 variant (NM_000535.7:c.2117del, p.Lys706Serfs*19) in 22 French-Canadian (FC) families from Quebec with Lynch syndrome (LS; n = 21) or constitutional mismatch repair deficiency (CMMRD; n = 1). We aimed to (a) confirm its founder origin, (b) assess its allele frequency in the FC population, and (c) determine its contribution to the risk of developing various cancers in this population. We identified a haplotype common to all c.2117del alleles spanning 666 kb to 1.37 Mb, confirming the founder nature of the variant. In affected cases, the variant was found in 0 out of 821 breast cancer cases, 8 out of 693 (1.15%) endometrial cancer (EC) cases, and 1 out of 191 (0.52%) colorectal cancer (CRC) cases. In unaffected persons, the variant was identified in 22/6347 newborns (0.32025-01-01T00:00:00Z2025 Dec2026-06-05T09:41:56.796Z2026-05-15T03:12:32.336ZS-EPMC125804814054600610.1111/cge.14784