ClinVar

Description

Variant summary: PALB2 c.353T>C (p.Ile118Thr) 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 2.1e-05 in 288088 control chromosomes (gnomAD, publications). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.353T>C has been reported in the literature in individuals affected with Breast Cancer (Dorling_2021, Decker_2017), however these reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. One co-occurrence with another pathogenic variant has been seen in our laboratory (CHEK2 c.1100delC, p.Thr367MetfsX15), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submitters have assessed the variant since 2014: all have classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.