ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7997C>A (p.Thr2666Asn)

gnomAD frequency: 0.00001  dbSNP: rs730881384
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159752 SCV000209768 likely pathogenic not provided 2023-09-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26633542, 32906206, 32832836)
Invitae RCV000628059 SCV000748948 pathogenic Ataxia-telangiectasia syndrome 2023-09-26 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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: 181984). This missense change has been observed in individual(s) with a disorder of the central nervous system, prostate cancer and/or ataxia-telangiectasia (PMID: 26633542, 32832836; external communication). It has also been observed to segregate with disease in related individuals. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2666 of the ATM protein (p.Thr2666Asn). This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV001027026 SCV001189520 likely pathogenic Hereditary cancer-predisposing syndrome 2022-09-20 criteria provided, single submitter clinical testing The p.T2666N variant (also known as c.7997C>A), located in coding exon 53 of the ATM gene, results from a C to A substitution at nucleotide position 7997. The threonine at codon 2666 is replaced by asparagine, an amino acid with similar properties. This alteration has been detected in an individual with an unspecified abnormality of the nervous system (Retterer K. et al. Genet. Med. 2016 07;18(7):696-704). In addition, this alteration has been detected in conjunction with another pathogenic ATM mutation in two individuals with clinical features consistent with ataxia telangiectasia (personal communication). 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, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Baylor Genetics RCV003467237 SCV004208230 likely pathogenic Familial cancer of breast 2023-10-17 criteria provided, single submitter clinical testing

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