ClinVar

Description

Variant summary: BRCA2 c.3515C>G (p.Ser1172Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250824 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.3515C>G, has been reported in the literature in individuals affected with Breast and Ovarian Cancer (Wong-Brown_2015, D'Argenio_2015, Delahunty_2022, Nguyen-Dumont_2020). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. 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: 25682074, 25896959, 35263119, 32772980). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified at VUS (n=5) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.