rs786204068

Description

Variant summary: The BRIP1 c.3215C>A (p.Thr1072Asn) variant involves the alteration of a non-conserved nucleotide and 3/5 in silico tools predict a benign outcome for this variant. However, these predictions have yet to be functionally assessed. This variant is absent in 121310 control chromosomes (ExAC). An internal LCA sample reports the variant to co-occur with a likely pathogenic PALB2 large deletion, c.49-10*10del (exons 2-13del) suggesting the variant is possibly benign. Although the variant of interest has not, to our knowledge, been reported in affected individuals via publications. A clinical diagnostic laboratory classifies the variant as "uncertain significance." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance - Possibly Benign," until additional information becomes available.

This sequence change replaces threonine with asparagine at codon 1072 of the BRIP1 protein (p.Thr1072Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This sequence change has not been published in the literature and is not present in population databases. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "deleterious"; MutationTaster: "polymorphism"; Align-GVGD: "C0"). In summary, this is a novel missense change. Although there is no indication that this sequence change affects protein function or causes disease, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.