rs786203344

Description

This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1047 of the BRIP1 protein (p.Leu1047Ser). This variant is present in population databases (rs786203344, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 186944). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The p.L1047S variant (also known as c.3140T>C), located in coding exon 19 of the BRIP1 gene, results from a T to C substitution at nucleotide position 3140. The leucine at codon 1047 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.