Submissions for variant NM_000051.4(ATM):c.7788+7G>A

gnomAD frequency: 0.00001  dbSNP: rs749610251

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554985	SCV000622775	likely benign	Ataxia-telangiectasia syndrome	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000606073	SCV000717695	likely benign	not specified	2017-03-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000776302	SCV000911609	likely benign	Hereditary cancer-predisposing syndrome	2017-01-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000606073	SCV000918566	uncertain significance	not specified	2018-09-28	criteria provided, single submitter	clinical testing	Variant summary: ATM c.7788+7G>A 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 8.1e-06 in 245476 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7788+7G>A in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Sema4, Sema4	RCV000776302	SCV002538182	likely benign	Hereditary cancer-predisposing syndrome	2021-02-05	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV004592534	SCV005081975	likely benign	Familial cancer of breast	2024-06-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.