ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8248T>A (p.Leu2750Ile)

dbSNP: rs876658559
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217852 SCV000273977 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-22 criteria provided, single submitter clinical testing The p.L2750I variant (also known as c.8248T>A), located in coding exon 55 of the ATM gene, results from a T to A substitution at nucleotide position 8248. The leucine at codon 2750 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast cancer (McDonald JT et al. PLoS One, 2022 Oct;17:e0273835). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001301600 SCV001490775 uncertain significance Ataxia-telangiectasia syndrome 2022-09-05 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 230427). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2750 of the ATM protein (p.Leu2750Ile).

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