ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6890A>C (p.Gln2297Pro)

dbSNP: rs1565520560
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687278 SCV000814837 uncertain significance Ataxia-telangiectasia syndrome 2023-04-06 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 567255). This missense change has been observed in individual(s) with ataxia-telangiectasia (PMID: 17376192). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2297 of the ATM protein (p.Gln2297Pro).
Ambry Genetics RCV003163112 SCV003866542 likely pathogenic Hereditary cancer-predisposing syndrome 2022-12-16 criteria provided, single submitter clinical testing The p.Q2297P variant (also known as c.6890A>C), located in coding exon 46 of the ATM gene, results from an A to C substitution at nucleotide position 6890. The glutamine at codon 2297 is replaced by proline, an amino acid with similar properties. This variant has been confirmed in trans with an ATM pathogenic variant in a Norwegian individual diagnosed with ataxia-telangiectasia (Stray-Pedersen A et al. Clin Exp Immunol, 2004 Jul;137:179-86). Internal structural analysis indicates this alteration is moderately disruptive to the FAT domain (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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