ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3449G>C (p.Arg1150Thr)

gnomAD frequency: 0.00018  dbSNP: rs555219189
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115177 SCV000149086 uncertain significance not provided 2021-04-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast or ovarian cancer (Singh 2018); This variant is associated with the following publications: (PMID: 29470806, 31919090)
Invitae RCV000199179 SCV000254084 likely benign Ataxia-telangiectasia syndrome 2022-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000215488 SCV000278041 likely benign Hereditary cancer-predisposing syndrome 2021-04-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000215488 SCV000687480 likely benign Hereditary cancer-predisposing syndrome 2020-10-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000115177 SCV001714396 uncertain significance not provided 2020-03-10 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818259 SCV002068402 uncertain significance not specified 2018-03-02 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000215488 SCV002536023 likely benign Hereditary cancer-predisposing syndrome 2021-12-05 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001818259 SCV002548067 likely benign not specified 2022-05-27 criteria provided, single submitter clinical testing Variant summary: ATM c.3449G>C (p.Arg1150Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 251216 control chromosomes, predominantly at a frequency of 0.0015 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM (0.001) causing an ATM-related Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.3449G>C has been reported in the literature as a VUS in settings of multigene panel testing among individuals with a variety of cancers to include breast cancer (example, Singh_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia Telangiectasia/ATM-related cancers. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (Likely benign, n=2; VUS, n=5). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc. RCV000199179 SCV001457147 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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.