ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6998C>T (p.Thr2333Ile) (rs150503164)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000590099 SCV000149149 uncertain significance not provided 2021-05-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with lung cancer (Parry 2017); This variant is associated with the following publications: (PMID: 21665257, 28843361)
Ambry Genetics RCV000115240 SCV000184909 likely benign Hereditary cancer-predisposing syndrome 2019-01-14 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
Invitae RCV000206376 SCV000259774 likely benign Ataxia-telangiectasia syndrome 2020-12-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000855568 SCV000694340 likely benign not specified 2021-06-05 criteria provided, single submitter clinical testing Variant summary: ATM c.6998C>T (p.Thr2333Ile) results in a non-conservative amino acid change located in the FAT domain (IPR003151) of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.4e-05 in 282418 control chromosomes (gnomAD), exclusively observed within the African or African-American subpopulation at a frequency of 0.00084. This frequency is somewhat smaller than expected maximum for a pathogenic variant in ATM causing Breast Cancer (0.001), allowing no conclusion about variant significance. However, this variant has also been reported in 6/2559 African American women (i.e. with an allele frequency of 0.0012) who were older than age 70 and cancer free (FLOSSIES database), supporting a benign role for the variant. The variant, c.6998C>T, has been reported in the literature in an individual affected with Lung adenocarcinoma (Parry_2017). This report does not provide unequivocal conclusions about association of the variant with Breast Cancer or Ataxia-Telangiectasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and reported the variant with conflicting assessments (likely benign, n=3; VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Color Health, Inc RCV000115240 SCV000910903 likely benign Hereditary cancer-predisposing syndrome 2016-04-22 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.