ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5824G>T (p.Ala1942Ser)

gnomAD frequency: 0.00001  dbSNP: rs1286443989
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000551414 SCV000622620 uncertain significance Ataxia-telangiectasia syndrome 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1942 of the ATM protein (p.Ala1942Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 453599). 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. This variant disrupts the p.Ala1942 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22649200, 24090759). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV000561691 SCV000660506 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-29 criteria provided, single submitter clinical testing The p.A1942S variant (also known as c.5824G>T), located in coding exon 38 of the ATM gene, results from a G to T substitution at nucleotide position 5824. The alanine at codon 1942 is replaced by serine, an amino acid with similar properties. Another variant at the same codon, p.A1942V (c.5825C>T), has been described in multiple probands with ataxia-telangiectasia (A-T) (Carney EF et al. J Immunol. 2012 Jul;189:261-8; Davis MY et al. J. Neurol. Sci. 2013 Dec;335:134-8), and demonstrated loss of kinase activity in functional assays (Carney EF et al. J Immunol. 2012 Jul;189:261-8). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004568681 SCV005057171 uncertain significance Familial cancer of breast 2023-12-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000551414 SCV001452330 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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