ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5692C>T (p.Arg1898Ter) (rs775036118)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571941 SCV000667807 pathogenic Hereditary cancer-predisposing syndrome 2018-09-06 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000571941 SCV000687636 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Counsyl RCV000671308 SCV000796269 pathogenic Ataxia-telangiectasia syndrome 2017-12-08 criteria provided, single submitter clinical testing
Invitae RCV000671308 SCV000956854 pathogenic Ataxia-telangiectasia syndrome 2019-10-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1898*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs775036118, ExAC 0.006%). This variant has been observed in individuals affected with ataxia-telangiectasia and breast cancer (PMID: 17124347, 25077176, 23454770, 25374739, 23322442, 28724667). ClinVar contains an entry for this variant (Variation ID: 482526). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000671308 SCV001158445 pathogenic Ataxia-telangiectasia syndrome 2019-05-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000671308 SCV001337784 pathogenic Ataxia-telangiectasia syndrome 2020-01-17 criteria provided, single submitter clinical testing Variant summary: ATM c.5692C>T (p.Arg1898X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant allele was found at a frequency of 8e-06 in 251006 control chromosomes (gnomAD). c.5692C>T has been reported in the literature in multiple individuals affected with Breast Cancer or Ataxia-Telangiectasia (eg. Magliozzi_2006, Micol_2011, Nespoli_2013, Nakamura_2014, Momozawa_2018, Wang_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.