ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2282_2283CT[1] (p.Leu762fs) (rs587781658)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129801 SCV000184612 pathogenic Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000129801 SCV000682047 pathogenic Hereditary cancer-predisposing syndrome 2016-12-05 criteria provided, single submitter clinical testing
Counsyl RCV000233154 SCV000485904 likely pathogenic Ataxia-telangiectasia syndrome 2016-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000480339 SCV000567457 pathogenic not provided 2019-01-07 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in ATM is denoted c.2284_2285delCT at the cDNA level and p.Leu762ValfsX2 (L762VfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CACT[delCT]GTTT. The deletion causes a frameshift, which changes a Leucine to a Valine at codon 762, and creates a premature stop codon at position 2 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. Also published as ATM c.2284delCT and c.2282_2283del using alternate nomenclature, this variant has been reported in the homozygous or compound heterozygous state in individuals with a clinical diagnosis of Ataxia-Telangiectasia and an infant with severe primary immunodeficiency (Gilad 1996, Stankovic 1998, Exley 2011, Reiman 2011, Yu 2016). It has also been observed in the single heterozygous state in at least one individual with breast or ovarian cancer as well as in a child with acute lymphoblastic leukemia (ALL) (Liberzon 2004, Thompson 2016). We consider this variant to be pathogenic.
GeneReviews RCV000233154 SCV000328299 pathogenic Ataxia-telangiectasia syndrome 2016-10-27 no assertion criteria provided literature only
Genetic Services Laboratory, University of Chicago RCV000233154 SCV000593514 pathogenic Ataxia-telangiectasia syndrome 2016-12-30 criteria provided, single submitter clinical testing
Invitae RCV000233154 SCV000282894 pathogenic Ataxia-telangiectasia syndrome 2018-12-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu762Valfs*2) 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 affected with ataxia-telangiectasia (PMID: 8789452, 8845835, 21792198, 9463314, 27484032). ClinVar contains an entry for this variant (Variation ID: 141325). 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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