ClinVar

Description

Variant summary: BRIP1 c.617C>T (p.Ser206Leu) results in a non-conservative amino acid change located in the Helicase superfamily 1/2, ATP-binding domain (IPR014001) of 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 1.6e-05 in 251312 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.617C>T has been reported in the literature in an individual affected with Breast Cancer (example, Weitzel_2019), and another individual affected with colorectal cancer (example, Fujita_2020), but was also found in controls (example, Ramus_2015, Dorling_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Breast Cancer. At-least two co-occurrences with other pathogenic variant(s) have been observed at our laboratory (BARD1 c.1872delT , p.Leu625SerfsX7 ; BRCA1 c.(4986+1_4987-1)_(5074+1_5075-1)del [exon 16 del]), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=5, Likely Benign, n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.