ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8793T>A (p.Cys2931Ter)

dbSNP: rs1555143494
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522033 SCV000617378 likely pathogenic not provided 2017-04-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.8793T>A at the cDNA level and p.Cys2931Ter (C2931X) at the protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon (TGT>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in an individual with Ataxia-telangiectasia who also carried a canonical splice variant in ATM; however, phase was not determined (Sandoval 1999). Based on currently available evidence, we consider ATM c.8793T>A to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000539551 SCV000622854 pathogenic Ataxia-telangiectasia syndrome 2023-06-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 449347). This premature translational stop signal has been observed in individual(s) with ataxia telangiectasia and/or breast cancer (PMID: 9887333, 26556299). This sequence change creates a premature translational stop signal (p.Cys2931*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).
Ambry Genetics RCV001018342 SCV001179568 pathogenic Hereditary cancer-predisposing syndrome 2022-09-13 criteria provided, single submitter clinical testing The p.C2931* pathogenic mutation (also known as c.8793T>A), located in coding exon 60 of the ATM gene, results from a T to A substitution at nucleotide position 8793. This changes the amino acid from a cysteine to a stop codon within coding exon 60. This alteration was reported in an individual with ataxia telangiectasia in conjunction with a canonical splice site alteration; however, the phase (whether in cis or trans) is not known (Sandoval N et al. Hum. Mol. Genet., 1999 Jan;8:69-79). 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.
Institute of Human Genetics, University of Leipzig Medical Center RCV001253612 SCV001429433 pathogenic Familial cancer of breast 2018-10-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001253612 SCV004931125 pathogenic Familial cancer of breast 2024-02-05 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
BRCAlab, Lund University RCV001253612 SCV002589047 pathogenic Familial cancer of breast 2022-08-26 no assertion criteria provided clinical testing

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