ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6807+1_6807+7del

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002369513 SCV002666317 likely pathogenic Hereditary cancer-predisposing syndrome 2021-04-08 criteria provided, single submitter clinical testing The c.6807+1_6807+7delGTAAATA intronic variant results from a deletion of 7 nucleotides between positions +1 and +7 and involves the canonical splice donor site after coding exon 45 of the ATM gene. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). The canonical splice donor site is highly conserved through marmoset. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish and weaken the native donor splice site, respectively. However, direct evidence is unavailable. 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 likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098389 SCV003211201 likely pathogenic Ataxia-telangiectasia syndrome 2022-06-16 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 46 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).

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