ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8146G>T (p.Val2716Phe) (rs730881385)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000159753 SCV000278266 likely pathogenic Hereditary cancer-predisposing syndrome 2015-09-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Well-characterized mutation at same position,Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000258960 SCV000209769 pathogenic not provided 2016-09-23 criteria provided, single submitter clinical testing The V2716F variant in the ATM gene has not been reported previously as a disease-causing variant nor as a benign polymorphism, to our knowledge. However, a different missense variant at this residue (V2716A) has been reported in association with ataxia-telangiectasia (Scott et al., 2002). The V2716F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V2716F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is well-conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (D2708N; D2708E; R2719H; A2726V) have been reported in association with ataxia-telangiectasia, supporting the functional importance of this region of the protein. We interpret V2716F as a disease-causing variant associated with ataxia-telangiectasia.

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