ClinVar

Description

This variant is denoted BRCA2 c.8708A>T at the cDNA level, p.Glu2903Val (E2903V) at the protein level, and results in the change of a Glutamic Acid to a Valine (GAG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu2903Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glutamic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu2903Val occurs at a position that is conserved across species and is located in the DNA binding domain (Borg 2010). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA2 Glu2903Val is pathogenic or benign. We consider it to be a variant of uncertain significance.