ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7792C>T (p.Arg2598Ter) (rs138941496)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564573 SCV000668152 pathogenic Hereditary cancer-predisposing syndrome 2017-08-16 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 RCV000564573 SCV000904736 pathogenic Hereditary cancer-predisposing syndrome 2017-11-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763225 SCV000893857 pathogenic Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000256020 SCV000322214 likely pathogenic not provided 2016-05-12 criteria provided, single submitter clinical testing This variant is denoted ATM c.7792C>T at the cDNA level and p.Arg2598Ter (R2598X) at the proteinlevel. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA),and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNAdecay. This variant has been observed in at least three ataxia-telangiectasia patients, 2 of whom were identified tocarry a second ATM truncating variant (Wright 1996, Mitui 2003, Lin 2015). We consider this variant to be likelypathogenic
Invitae RCV000705286 SCV000834275 pathogenic Ataxia-telangiectasia syndrome 2018-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2598*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs138941496, ExAC 0.002%). This variant has been reported in several individuals affected with ataxia-telangiectasia (PMID: 8808599, 12815592, 10864201, 26677768) and observed on the opposite chromosome (in trans) from other pathogenic variants in most of the affected individuals (PMID: 12815592, 10864201, 26677768). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 265383). 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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