rs587780249

Description

The p.D1138Y variant (also known as c.3412G>T), located in coding exon 19 of the BRIP1 gene, results from a G to T substitution at nucleotide position 3412. The aspartic acid at codon 1138 is replaced by tyrosine, an amino acid with highly 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.

This variant is denoted BRIP1 c.3412G>T at the cDNA level, p.Asp1138Tyr (D1138Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). This variant was observed in an individual with head and neck squamous cell carcinoma (Lu 2015). BRIP1 Asp1138Tyr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Asp1138Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.