ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7566A>G (p.Gln2522=) (rs775621333)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206378 SCV000260869 uncertain significance Ataxia-telangiectasia syndrome 2020-10-29 criteria provided, single submitter clinical testing This sequence change affects codon 2522 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. This variant is present in population databases (rs775621333, ExAC 0.05%). This variant has been observed in individual(s) with breast cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 220378). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV000483209 SCV000565740 uncertain significance not provided 2020-10-28 criteria provided, single submitter clinical testing In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in individuals with breast cancer, but also in unaffected controls (Chan 2018, Momozawa 2018); This variant is associated with the following publications: (PMID: 29338689, 30287823, 30093976)
Ambry Genetics RCV000574825 SCV000660454 likely benign Hereditary cancer-predisposing syndrome 2019-12-11 criteria provided, single submitter clinical testing RNA Studies
Color Health, Inc RCV000574825 SCV000904734 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-02 criteria provided, single submitter clinical testing This synonymous variant does not change the amino acid sequence of the ATM protein, but it causes an A to G substitution in exon 51 of the ATM gene. Splice site prediction tools suggest that this variant may create a new splice acceptor site, although this prediction has not been confirmed in published RNA studies. This variant has been reported both in affected and unaffected individuals in a breast cancer risk case-control study (PMID: 30287823). This variant has been identified in 6/251308 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193662 SCV001362656 likely benign not specified 2019-10-03 criteria provided, single submitter clinical testing

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