ClinVar

Description

Variant summary: ATM c.4802G>A (p.Ser1601Asn) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251834 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4802G>A has been reported in the literature in individuals with a variety of ATM-related cancers such as BRCA1/2-negative breast cancer, 11q deletion Chronic Lymphocytic Leukemia (CLL) (example, Pagila_2010, Skowronska_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia/Breast/ATM-related cancers. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories and the Spanish ATM Cancer Susceptibility Variant Interpretation Working Group have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple submitters reported the variant with conflicting assessments (VUS, n=4; likely benign, n=4). Based on the evidence outlined above, the variant was classified as uncertain significance.