ClinVar

Description

Variant summary: ATM c.6572+4T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.6e-05 in 251458 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6572+4T>C has been reported in the literature as a VUS in settings of multigene panel testing in individuals affected undergoing testing for Lynch syndrome (example, Yurgelun_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia or other ATM-related cancers such as Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 135772). Based on the evidence outlined above, the variant was classified as likely benign.