ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6541G>A (p.Glu2181Lys)

dbSNP: rs2136242185
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Centre For Genomic Medicine, NCGM RCV001823617 SCV002073198 uncertain significance Ataxia-telangiectasia syndrome criteria provided, single submitter clinical testing The missense variant p.E2181K in ATM (NM_000051.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.E2181K variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.E2181K missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glutamic acid residue at codon 2181 of ATM is conserved in all mammalian species. The nucleotide c.6541 in ATM is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001823617 SCV002297725 uncertain significance Ataxia-telangiectasia syndrome 2023-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2181 of the ATM protein (p.Glu2181Lys). 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: 1339163). 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.
Ambry Genetics RCV002361081 SCV002660868 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-27 criteria provided, single submitter clinical testing The p.E2181K variant (also known as c.6541G>A), located in coding exon 44 of the ATM gene, results from a G to A substitution at nucleotide position 6541. The glutamic acid at codon 2181 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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