ClinVar

Description

This deletion of 4 nucleotides in BRCA2 is denoted c.9939_9942delGAAA at the cDNA level and p.Lys3315AsnfsX2 (K3315NfsX2) at the protein level. The normal sequence, with the bases that are deleted in braces, is TAAA[GAAA]AAAG. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 3315, and creates a premature stop codon at position 2 of the new reading frame. This variant has not, to our knowledge, been reported in the literature as pathogenic or benign. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Although this variant results in a frameshift and premature stop codon, it is located just upstream of a well-known polymorphism that also results in a premature stop of translation (K3326X), suggesting that this region of the BRCA2 gene and the region beyond codon 3326 is not crucial for proper function. Based on currently available information, it is unclear whether this deletion is pathogenic or benign. We consider it to be a variant of uncertain significance.