ClinVar

Description

Variant summary: BRCA2 c.5590G>A (p.Asp1864Asn) results in a conservative amino acid change located in the BRCA2 repeat (IPR002093) of 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 1.9e-05 in 268772 control chromosomes (gnomAD, Dong_2021). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5590G>A has been reported in the literature in individuals affected with esophageal cancer (Zhong_2011), and Breast/Ovarian cancer (Zhong_2016, Cao_2016, Park_2017, So_2019, Dorling_2021). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. A multi-factorial analysis of ethnic Koreans by Lee_2018 produced a combined likelihood ratio of 0.023, leading the authors to conclude the variant is "likely benign". To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed the variant since 2014: all have classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.