ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8105T>G (p.Ile2702Arg)

gnomAD frequency: 0.00001  dbSNP: rs876659735
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215525 SCV000276518 likely pathogenic Hereditary cancer-predisposing syndrome 2022-01-06 criteria provided, single submitter clinical testing The p.I2702R variant (also known as c.8105T>G), located in coding exon 54 of the ATM gene, results from a T to G substitution at nucleotide position 8105. The isoleucine at codon 2702 is replaced by arginine, an amino acid with similar properties. This alteration has been detected in an individual with ataxia telangiectasia (A-T) in conjunction with an additional ATM pathogenic mutation, and p.I2702R has been associated with absent ATM protein and/or absent p53 kinase activity (Sun X et al. J Pediatr, 2002 Jun;140:724-31; Becker-Catania SG et al. Mol. Genet. Metab. 2000 Jun; 70(2):122-33; Mitui M et al, Hum. Mutat. 2003 Jul; 22(1):43-50). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000800002 SCV000939698 likely pathogenic Ataxia-telangiectasia syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2702 of the ATM protein (p.Ile2702Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ataxia-telangiectasia (PMID: 12815592). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 232389). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV000800002 SCV002076896 uncertain significance Ataxia-telangiectasia syndrome 2020-08-26 no assertion criteria provided clinical testing

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