ClinVar

Description

Variant summary: BRCA2 c.2471T>C (p.Leu824Ser) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-06 in 237562 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2471T>C has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome, often reported as a VUS (examples: Li_2017, Kwong_2020, Guo_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31837001, 32068069, 28664449). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories classified the variant as likely benign (n=1), uncertain significance (n=3), or likely pathogenic (n=1) . Based on the evidence outlined above, the variant was classified as uncertain significance.