ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.9145_9146del (p.Phe3049fs) (rs1555152058)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000628183 SCV000749076 likely pathogenic Ataxia-telangiectasia syndrome 2017-10-02 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ATM gene (p.Phe3049Profs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acids of the ATM protein and extend the length of the ATM protein by 5 amino acid residues. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with ataxia-telangiectasia (PMID: 10817650). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant disrupts a portion of the FATC domain, which spans the last 33 amino acids of the ATM protein (PMID: 19781682). A experimental study has shown that the entire FATC domain is required for ATM kinase activity in response to DNA damage (PMID: 16603769). 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.

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