ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1139_1142dup (p.Ser381fs) (rs886041340)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000285085 SCV000329804 likely pathogenic not provided 2016-07-18 criteria provided, single submitter clinical testing This duplication of four nucleotides in ATM is denoted c.1139_1142dupACAG at the cDNA level and p.Ser381ArgfsX27 (S381RfsX27) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is GATT[dupACAG]TGTC. The duplication causes a frameshift which changes a Serine to an Arginine at codon 381, and creates a premature stop codon at position 27 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.1139_1142dupACAG, published as c.1141insGACA using alternate nomenclature, has been observed in the compound heterozygous state in at least one patient with ataxia-telangiectasia (Hacia 1998). Based on the currently available information, we consider this duplication to be a likely pathogenic variant.
Invitae RCV000475637 SCV000546710 pathogenic Ataxia-telangiectasia syndrome 2019-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser381Argfs*27) 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 observed in individual(s) with ataxia-telangiectasia (PMID: 9872980). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 280044). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000493506 SCV000581441 pathogenic Hereditary cancer-predisposing syndrome 2019-03-28 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 RCV000475637 SCV000694172 pathogenic Ataxia-telangiectasia syndrome 2016-08-24 criteria provided, single submitter clinical testing Variant summary: The ATM c.1139_1142dupACAG (p.Ser381Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent ATM 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 (e.g. p.Trp393X, p.Gln1017X, p.Arg1466X, p.Tyr2755fs). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 121144 control chromosomes, but has been cited in at least one AT patients in the literature. Taken together, this variant is classified as pathogenic.
Color RCV000493506 SCV001357904 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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