ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7847T>C (p.Met2616Thr)

gnomAD frequency: 0.00001  dbSNP: rs762765902
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217366 SCV000276413 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-17 criteria provided, single submitter clinical testing The p.M2616T variant (also known as c.7847T>C), located in coding exon 52 of the ATM gene, results from a T to C substitution at nucleotide position 7847. The methionine at codon 2616 is replaced by threonine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000217366 SCV000904738 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 2616 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has been identified in 2/282308 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001233269 SCV001405856 uncertain significance Ataxia-telangiectasia syndrome 2024-11-03 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2616 of the ATM protein (p.Met2616Thr). This variant is present in population databases (rs762765902, gnomAD 0.003%). 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: 232313). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATM protein function. 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.
Natera, Inc. RCV001233269 SCV002075887 uncertain significance Ataxia-telangiectasia syndrome 2020-08-19 no assertion criteria provided clinical testing

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