ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7456C>T (p.Arg2486Ter) (rs587779865)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115251 SCV000213694 pathogenic Hereditary cancer-predisposing syndrome 2017-06-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000212068 SCV000780405 likely pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000212068 SCV000149160 pathogenic not provided 2017-11-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.7456C>T at the cDNA level and p.Arg2486Ter (R2486X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM Arg2486Ter has been reported in patients with breast or pancreatic cancer and in the homozygous and compound heterozygous states in individuals with Ataxia-telangiectasia (Buzin 2003, Meneret 2014, Susswein 2016, Takai 2016). We therefore consider this variant to be pathogenic.
Invitae RCV000462583 SCV000547106 pathogenic Ataxia-telangiectasia syndrome 2018-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2486*) 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 been reported as heterozygous in an individual with breast cancer (PMID: 26681312), and as homozygous in an individual with ataxia-telangiectasia (PMID: 12552559). ClinVar contains an entry for this variant (Variation ID: 127445). Loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). For these reasons, this variant has been classified as Pathogenic.

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