ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3154-5C>T

gnomAD frequency: 0.00004  dbSNP: rs55719759
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129749 SCV000184555 likely benign Hereditary cancer-predisposing syndrome 2018-10-19 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.
Invitae RCV000462650 SCV000558392 likely benign Ataxia-telangiectasia syndrome 2024-01-30 criteria provided, single submitter clinical testing
Mendelics RCV000462650 SCV000838517 benign Ataxia-telangiectasia syndrome 2023-08-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000129749 SCV000911173 likely benign Hereditary cancer-predisposing syndrome 2015-04-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779795 SCV000916599 likely benign not specified 2023-03-13 criteria provided, single submitter clinical testing Variant summary: ATM c.3154-5C>T 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 0.00047 in 328526 control chromosomes, predominantly in Japanese population (0.0019). This frequency is slightly higher than estimated for a pathogenic variant in ATM causing Breast Cancer (0.001), suggesting this variant may be benign. c.3154-5C>T has been reported in the literature in individuals affected with Breast Cancer. These reports 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. 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 (benign/likely benign n=4, VUS n=3). Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV001311785 SCV001884257 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29338689)
Sema4, Sema4 RCV000129749 SCV002533598 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-06 criteria provided, single submitter curation
Athena Diagnostics Inc RCV001311785 SCV002771626 uncertain significance not provided 2022-06-14 criteria provided, single submitter clinical testing

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