ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8787-1G>A

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002373660 SCV002687872 pathogenic Hereditary cancer-predisposing syndrome 2020-06-02 criteria provided, single submitter clinical testing The c.8787-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 60 of the ATM gene. RNA studies have demonstrated that a different nucleotide change at the same position, c.8787-1G>C, results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV002508851 SCV002818268 pathogenic not provided 2022-12-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003605832 SCV004515380 likely pathogenic Ataxia-telangiectasia syndrome 2023-02-11 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 60 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 1764649). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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