ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8140C>T (p.Gln2714Ter) (rs1060501695)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480590 SCV000566956 pathogenic not provided 2016-05-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.8140C>T at the cDNA level and p.Gln2714Ter (Q2714X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in the compound heterozygous and homozygous state in cases of classical Ataxia-Telangiectasia, with analyses of the compound heterozygous lymphoblastoid cell line showing significantly decreased mRNA expression and increased radiosensitivity (Gilad 1996, Fernet 2003, Angele 2004, Gutierrez-Enriquez 2004, Cavaciuti 2005). Based on the currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000627965 SCV000748851 pathogenic Ataxia-telangiectasia syndrome 2017-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2714*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the homozygous state an individual affected with ataxia-telangiectasia (PMID: 8845835). ClinVar contains an entry for this variant (Variation ID: 419265). Experimental studies in heterozygous cell lines have suggested that this sequence change leads to reduced ATM protein following exposure to radiation (PMID: 14970866). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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