ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.237del (p.Lys79fs) (rs730881303)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159632 SCV000209620 pathogenic not provided 2021-07-23 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 23807571, 25614872, 30639167, 26681312)
Invitae RCV000548948 SCV000622324 pathogenic Ataxia-telangiectasia syndrome 2020-09-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys79Asnfs*37) 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 an individual affected with ovarian cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 181874). 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 RCV000570996 SCV000660499 pathogenic Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing The c.237delA pathogenic mutation, located in coding exon 3 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 237, causing a translational frameshift with a predicted alternate stop codon (p.K79Nfs*37). This alteration has been previously reported in an individual diagnosed with ovarian cancer (Susswein LR et al. Genet. Med. 2016 Aug;18:823-32). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Color Health, Inc RCV000570996 SCV000687382 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000548948 SCV000694219 likely pathogenic Ataxia-telangiectasia syndrome 2017-03-03 criteria provided, single submitter clinical testing Variant summary: The ATM c.237delA (p.Lys79Asnfs) 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.Tyr171X, p.Arg2993X, p.Lys2756X, etc.). This variant is absent in 114158 control chromosomes from ExAC. This variant has previously been reported in one A-T patient in compound heterozygous state with p.Tyr124Ter (Minto et al. 2017; a conference meeting abstract) and in one ovarian cancer patient (Susswein_2015). One clinical diagnostic laboratory has classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.

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