ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1607+5G>A

dbSNP: rs766535949
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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 RCV000777657 SCV000913547 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-07 criteria provided, single submitter clinical testing This variant causes a G>A nucleotide substitution at the +5 position of intron 10 of the ATM gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing, however, this prediction has not been confirmed in published RNA studies. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/249912 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000820970 SCV000961709 uncertain significance Ataxia-telangiectasia syndrome 2024-05-21 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs766535949, gnomAD 0.003%). 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: 631433). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000777657 SCV001172789 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-19 criteria provided, single submitter clinical testing The c.1607+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 9 in the ATM gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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