ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8585-2A>C (rs1060501700)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462876 SCV000547126 likely pathogenic Ataxia-telangiectasia syndrome 2019-10-09 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 58 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with ataxia-telangectasia (PMID: 23322442). ClinVar contains an entry for this variant (Variation ID: 407718). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). 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.
GeneDx RCV000482474 SCV000568339 likely pathogenic not provided 2017-01-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.8585-2A>C or IVS58-2A>C and consists of an A>C nucleotide substitution at the -2 position of intron 58 of the ATM gene. This 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 reported in the homozygous state in an individual with Ataxia-Telangiectasia (Jeddane 2013). Based on the currently available information, we consider ATM c.8585-2A>C to be a likely pathogenic variant.
Mendelics RCV000462876 SCV001138582 likely pathogenic Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001018039 SCV001179217 pathogenic Hereditary cancer-predisposing syndrome 2019-10-01 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation

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