ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8810T>C (p.Val2937Ala) (rs587782149)

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 RCV000130713 SCV000185600 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130713 SCV000682519 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing
Counsyl RCV000456899 SCV000797615 uncertain significance Ataxia-telangiectasia syndrome 2018-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000236232 SCV000292486 uncertain significance not provided 2018-02-23 criteria provided, single submitter clinical testing This variant is denoted ATM c.8810T>C at the cDNA level, p.Val2937Ala (V2937A) at the protein level, and results in the change of a Valine to an Alanine (GTG>GCG). This variant was observed in a patient with chronic lymphocytic leukemia (Mansouri 2014). ATM Val2937Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the kinase domain (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 Val2937Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000779797 SCV000916601 uncertain significance not specified 2018-10-22 criteria provided, single submitter clinical testing Variant summary: ATM c.8810T>C (p.Val2937Ala) results in a non-conservative amino acid change located in the Phosphatidylinositol 3-/4-kinase, catalytic domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 30974 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8810T>C has been reported in the literature in an individual affected with CLL (Mansouri_2013). These report(s) do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000456899 SCV000546673 uncertain significance Ataxia-telangiectasia syndrome 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 2937 of the ATM protein (p.Val2937Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with chronic lymphocytic leukemia (PMID: 24172824). ClinVar contains an entry for this variant (Variation ID: 141968). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.