ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3756T>A (p.Tyr1252Ter) (rs886039637)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255522 SCV000322565 likely pathogenic not provided 2017-12-12 criteria provided, single submitter clinical testing This variant is denoted ATM c.3756T>A at the cDNA level and p.Tyr1252Ter (Y1252X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in a leiomyosarcoma (Helsten 2015). Based on currently available evidence, we consider this variant to be likely pathogenic.
Ambry Genetics RCV000569538 SCV000665654 pathogenic Hereditary cancer-predisposing syndrome 2018-12-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Counsyl RCV000665264 SCV000789355 likely pathogenic Ataxia-telangiectasia syndrome 2017-01-26 criteria provided, single submitter clinical testing
Color RCV000569538 SCV000903427 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV000665264 SCV001390925 pathogenic Ataxia-telangiectasia syndrome 2019-11-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1252*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 265575). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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