ClinVar

Description

Variant summary: BRCA2 c.2837A>G (p.Asp946Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250610 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2837A>G has been reported in the literature in at least one individual affected with breast cancer (Encinas_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variant(s) in the NHGRI BIC database have been reported (BRCA2 c.5454delA, p.Cys1820AlafsX20), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (Biswas_2023). These results showed no damaging effect of this variant. The following publications have been ascertained in the context of this evaluation (PMID: 37922907, 20858050, 29854292, 23929434). ClinVar contains an entry for this variant (Variation ID: 51358). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.