ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.663-2A>G (rs886041931)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000387350 SCV000330736 likely pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing This variant is denoted ATM c.663-2A>G or IVS6-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 6 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 not, to our knowledge, been published in the literature. Based on the currently available information, we consider ATM c.663-2A>G to be a likely pathogenic variant.
Counsyl RCV000669607 SCV000794378 likely pathogenic Ataxia-telangiectasia syndrome 2017-10-06 criteria provided, single submitter clinical testing
Invitae RCV000669607 SCV001576515 likely pathogenic Ataxia-telangiectasia syndrome 2020-08-23 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 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 not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 280786). 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.

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