ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4109+6T>C

gnomAD frequency: 0.00005  dbSNP: rs368606937
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000196920 SCV000254100 likely benign Ataxia-telangiectasia syndrome 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000588070 SCV000278824 uncertain significance not provided 2021-09-10 criteria provided, single submitter clinical testing In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12553040)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001530925 SCV000694273 likely benign not specified 2021-06-21 criteria provided, single submitter clinical testing Variant summary: ATM c.4109+6T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.8e-05 in 248012 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Ataxia-Telangiectasia (4.8e-05 vs 0.004), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.4109+6T>C in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Five 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 with a majority peer consensus leaning towards a likely benign outcome (n=3) (VUS, n=2). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences RCV000588070 SCV000805554 likely benign not provided 2018-01-12 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776097 SCV000910905 likely benign Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004589864 SCV005084505 likely benign Familial cancer of breast 2024-05-22 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Natera, Inc. RCV000196920 SCV001462141 uncertain significance Ataxia-telangiectasia syndrome 2020-01-08 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.