ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5890A>T (p.Lys1964Ter) (rs201963507)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159769 SCV000209790 likely pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing This likely pathogenic variant is denoted ATM c.5890A>T at the cDNA level and p.Lys1964Ter (K1964X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in the compound heterozygous state in a case of Ataxia Telangiectasia (Du 2008) and is considered likely pathogenic.
Invitae RCV000206728 SCV000261307 pathogenic Ataxia-telangiectasia syndrome 2020-07-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1964*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in an individual affected with ataxia-telangiectasia (PMID: 18321536). ClinVar contains an entry for this variant (Variation ID: 182000). 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 RCV000570753 SCV000667830 pathogenic Hereditary cancer-predisposing syndrome 2017-02-13 criteria provided, single submitter clinical testing The p.K1964* pathogenic mutation (also known as c.5890A>T), located in coding exon 38 of the ATM gene, results from an A to T substitution at nucleotide position 5890. This changes the amino acid from a lysine to a stop codon within coding exon 38. This alteration has been reported in a compound heterozygous state in an individual affected with ataxia-telangiectasia (Du L et al. Mutat. Res., 2008 Apr;640:139-44). 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 RCV000570753 SCV000682289 pathogenic Hereditary cancer-predisposing syndrome 2020-12-03 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 39 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in trans with another ATM mutation in an individual affected with ataxia-telangiectasia (PMID: 18321536). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Counsyl RCV000206728 SCV000799227 likely pathogenic Ataxia-telangiectasia syndrome 2018-04-11 criteria provided, single submitter clinical testing

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