ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8156G>A (p.Arg2719His) (rs55982963)

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
Ambry Genetics RCV000115262 SCV000184388 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000115262 SCV000682464 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-16 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000232453 SCV000745134 uncertain significance Ataxia-telangiectasia syndrome 2016-07-27 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000232453 SCV000734791 uncertain significance Ataxia-telangiectasia syndrome no assertion criteria provided clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764949 SCV000896121 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000586113 SCV000149171 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.8156G>A at the cDNA level, p.Arg2719His (R2719H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has been reported in individuals with suspected hereditary breast/ovarian cancer as well as in an individual with urothelial bladder cancer (Brunet 2008, Balb?s-Mart?nez 2013, Maxwell 2016, Mucaki 2016). ATM Arg2719His was observed at an allele frequency of 0.051%, (17/33,528) in individuals of Latino ancestry in large population cohorts (Lek 2016). ATM Arg2719His is located in the ATP binding domain within the kinase domain (Lavin 2004, Stracker 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Arg2719His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000586113 SCV000694372 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The c.8156G>A (p.Arg2719His) in ATM gene is a missense change that involves a conserved nucleotide and 4/5 in silico tools predict deleterious outcome. The variant is located in the PI3/PI4-kinase domain, however no functional studies confirming deleterious effect of this change have been reported at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.00017 (20/116502 chrs tested), predominantly in individuals of Latino descent (0.0017; 13/1130chrs tested), including 1 homozygote. The latter frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.0010, suggesting it is may be an ethnic-specific functional polymorphism. The variant has been reported in BrC pts without strong evidence for causality. The variant is cited as VUS by a reputable databases/clinical laboratories without evidence to independently evaluate. Taking together, the variant was classified as VUS.
Invitae RCV000232453 SCV000283074 uncertain significance Ataxia-telangiectasia syndrome 2019-01-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2719 of the ATM protein (p.Arg2719His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs55982963, ExAC 0.1%). This variant has been observed in individuals affected with breast cancer (PMID: 18384426, 19781682, 21445571). ClinVar contains an entry for this variant (Variation ID: 127456). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000232453 SCV000838607 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter 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.