Submissions for variant NM_000051.4(ATM):c.2960G>A (p.Cys987Tyr)

dbSNP: rs1555085052

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000627999	SCV000748886	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 987 of the ATM protein (p.Cys987Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 524310). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV002279449	SCV002567267	uncertain significance	not provided	2022-02-21	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994051	SCV004813538	uncertain significance	not specified	2024-02-21	criteria provided, single submitter	clinical testing	Variant summary: ATM c.2960G>A (p.Cys987Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251326 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2960G>A in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 524310). Based on the evidence outlined above, the variant was classified as uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000627999	SCV002568355	likely pathogenic	Ataxia-telangiectasia syndrome	2021-06-25	no assertion criteria provided	clinical testing	We have seen this homozygously in a patient with clinical diagnosis of Ataxia-telangiectasia Syndrome (internal data).