ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.902-1G>T (rs1064793518)

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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 RCV000493667 SCV000581462 pathogenic Hereditary cancer-predisposing syndrome 2016-12-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Functionally-validated splicing mutation
Color RCV000493667 SCV000911165 pathogenic Hereditary cancer-predisposing syndrome 2017-11-17 criteria provided, single submitter clinical testing
GeneDx RCV000478968 SCV000566311 pathogenic not provided 2018-11-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.902-1G>T or IVS7-1G>T and consists of a G>T nucleotide substitution at the -1 position of intron 7 of the ATM gene. 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. Also published as IVS9-1G>T using alternate exon numbering, this variant has been observed in the compound heterozygous state in a case of Ataxia-Telangiectasia (Teraoka 1999). It has also been observed in an individual with family history of pancreatic cancer (Barnes 2017). Based on currently available evidence, we consider ATM c.902-1G>T to be pathogenic.
Invitae RCV000685477 SCV000812959 pathogenic Ataxia-telangiectasia syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 7 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 an individual affected with ataxia-telangiectasia in whom it co-occurs with a second pathogenic ATM variant (PMID: 10330348). This variant is also known as ISV9-1G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 418911). An experimental study using a B-lymphoblastoid cell line derived from an affected individual showed that this sequence change results in aberrant splicing (PMID: 10330348). 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). For these reasons, this variant has been classified as Pathogenic.

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