ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4910-2A>T

dbSNP: rs1555103156
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000581766 SCV000687582 likely pathogenic Hereditary cancer-predisposing syndrome 2022-01-31 criteria provided, single submitter clinical testing This variant causes an A to T nucleotide substitution at the -2 position of intron 32 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001377222 SCV001574497 likely pathogenic Ataxia-telangiectasia syndrome 2020-07-26 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 32 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: 490589). 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.
Ambry Genetics RCV000581766 SCV002646098 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-17 criteria provided, single submitter clinical testing The c.4910-2A>T intronic variant results from an A to T substitution two nucleotides upstream from coding exon 32 in the ATM gene. This nucleotide position is highly conserved in available vertebrate species. This alteration disrupts the canonical splice site, is expected to produce an in-frame transcript, and may lead to a clinically viable protein; however, direct evidence is unavailable at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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