ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7999A>T (p.Met2667Leu)

dbSNP: rs34099398
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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 RCV000565488 SCV000660690 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-15 criteria provided, single submitter clinical testing The p.M2667L variant (also known as c.7999A>T), located in coding exon 53 of the ATM gene, results from an A to T substitution at nucleotide position 7999. The methionine at codon 2667 is replaced by leucine, an amino acid with highly similar properties. This alteration was identified in 1/1207 cases of French women diagnosed with breast cancer who had a sister with breast cancer and were BRCA1 and BRCA2 negative and 0/1199 general population controls (Girard E et al. Int J Cancer, 2019 04;144:1962-1974). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000806156 SCV000946139 uncertain significance Ataxia-telangiectasia syndrome 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2667 of the ATM protein (p.Met2667Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30303537). ClinVar contains an entry for this variant (Variation ID: 479035). 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 tolerated. 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.
Baylor Genetics RCV003459273 SCV004213935 uncertain significance Familial cancer of breast 2022-01-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000806156 SCV002076818 uncertain significance Ataxia-telangiectasia syndrome 2020-08-26 no assertion criteria provided clinical testing

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