ClinVar Miner

Submissions for variant NM_001330368.2(C11orf65):c.641-18608_641-18607del (rs864622416)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205757 SCV000260560 pathogenic Ataxia-telangiectasia syndrome 2019-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys2337Serfs*35) 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 individuals with ataxia-telangiectasia (PMID: 9443866, 25614872, 16266405, 8659541). This variant is also known as 7009delTG in the literature. ClinVar contains an entry for this variant (Variation ID: 220198). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000484538 SCV000568331 pathogenic not provided 2016-06-07 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in ATM is denoted c.7010_7011delGT at the cDNA level and p.Cys2337SerfsX35 (C2337SfsX35) at the protein level. The normal sequence, with the bases that are deleted in braces, is GAAT[GT]CTGA. The deletion causes a frameshift which changes a Cysteine to a Serine at codon 2337, and creates a premature stop codon at position 35 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.7010_7011delGT has been reported in the compound heterozygous state in several individuals with Ataxia Telangiectasia, including confirmed classical phenotypes, and has been noted as a recurrent pathogenic variant in the Polish population (Telatar 1996, Mitui 2005, Podralska 2014). We consider this variant to be pathogenic.
Ambry Genetics RCV001025926 SCV001188208 pathogenic Hereditary cancer-predisposing syndrome 2019-05-31 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Integrated Genetics/Laboratory Corporation of America RCV000205757 SCV001370550 pathogenic Ataxia-telangiectasia syndrome 2020-05-01 criteria provided, single submitter clinical testing Variant summary: ATM c.7010_7011delGT (p.Cys2337SerfsX35) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251078 control chromosomes (gnomAD). c.7010_7011delGT has been reported in the literature in multiple individuals affected with Ataxia-Telangiectasia (Telatar_1996, Telatar_1998, Li_2000, Buzin_2003, Podralska_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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