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 2018-04-20 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.237delA at the cDNA level and p.Lys79AsnfsX37 (K79NfsX37) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAAA[delA]CCAA. The deletion causes a frameshift which changes a Lysine to an Asparagine at codon 79, and creates a premature stop codon at position 37 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.237delA was identified in at least one individual with ovarian cancer (Susswein 2016). We consider this variant to be pathogenic.
Invitae RCV000548948 SCV000622324 pathogenic Ataxia-telangiectasia syndrome 2019-11-25 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 Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000570996 SCV000687382 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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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