ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6976-2A>C (rs587782403)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131437 SCV000186419 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
GeneDx RCV000212053 SCV000209635 likely pathogenic not provided 2018-05-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.6976-2A>C or IVS47-2A>C and consists of an A>C nucleotide substitution at the -2 position of intron 47 of the ATM gene. Using alternate intron numbering, this variant would be defined as ATM IVS49-2A>C. The variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been observed in at least two individuals with breast cancer (Decker 2017). Based on the currently available information, we consider ATM c.6976-2A>C to be a likely pathogenic variant.
Invitae RCV000228133 SCV000283030 likely pathogenic Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 47. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in an individual with polyposis and colon cancer (PMID: 26681312). In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 18321536). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
Counsyl RCV000228133 SCV000486609 likely pathogenic Ataxia-telangiectasia syndrome 2016-07-05 criteria provided, single submitter clinical testing
Color RCV000131437 SCV000687745 likely pathogenic Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing

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