ClinVar

Description

The p.Glu3002Lys variant has been reported in the literature in 10/2398 proband chromosomes of individuals with hereditary breast cancer. It was not, however, detected in any of the 200 control chromosomes tested (Biswas_2012, Cavallone_2010, Cote_2012, Mondal_2012, Salazar_2006). It has also been reported in the UMD (x2), LOVD, BIC (x9) and BOCs databases. It is listed in the dbSNP database (ID#:rs80359152) but no frequency information was provided, and so the prevalence of this variant in the general population is not known. The p.Glu3002 residue is conserved across mammals and computational analyses (PolyPhen, SIFT, AlignGVGD) suggest that the p.Glu3002Lys variant may impact the protein. However, this information is not predictive enough to assume pathogenicity. Yet, functional studies have shown that compared to the wild-type protein, the variant affects the integrity of cytokinesis during the cell cycle, and that the DNA repair capacity of the mutant allele is compromised (Biswas_2012, Mondal_2012). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as predicted pathogenic.