ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8850+4A>C

gnomAD frequency: 0.00001  dbSNP: rs587782335
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131263 SCV000186228 likely benign Hereditary cancer-predisposing syndrome 2019-11-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000212091 SCV000209665 uncertain significance not provided 2023-11-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Observed in an individual with breast cancer in the published literature (PMID: 28779002); This variant is associated with the following publications: (PMID: 28779002)
Labcorp Genetics (formerly Invitae), Labcorp RCV000227772 SCV000283087 likely benign Ataxia-telangiectasia syndrome 2024-12-17 criteria provided, single submitter clinical testing
Counsyl RCV000227772 SCV000790694 uncertain significance Ataxia-telangiectasia syndrome 2017-04-05 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131263 SCV001348007 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-15 criteria provided, single submitter clinical testing This variant causes an A to C nucleotide substitution at the +4 position of intron 61 of the ATM gene. Splice site prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 6/251248 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493456 SCV004242563 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000131263 SCV005688872 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-09 criteria provided, single submitter clinical testing The splice region variant NM_000051.4(ATM):c.8850+4A>C has not been reported previously as a pathogenic variant, to our knowledge. The c.8850+4A>C variant is not predicted to disrupt the existing donor splice site 2bp upstream by any splice site algorithm. The c.8850+4A>C variant is predicted to introduce a novel splice site by 1 of 4 splice site algorithms. The c.8850+4A>C variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Uncertain Significance.

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