ClinVar

Description

Variant summary: BRCA2 c.2716A>G (p.Thr906Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 250434 control chromosomes (gnomAD and Guo_2020). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2716A>G has been reported in the literature as a non-informative genotype in at-least one patient with Ovarian adenocarcinoma (Aref-Eshghi_2020). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant has been reported (BRCA1 c.3664G>T, p.Glu1222X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1) or likely benign (n=4). Based on the lack of evidence supporting an actionable outcome as outlined above, the variant was classified as likely benign to reflect the prevailing peer consensus.