Submissions for variant NM_000051.4(ATM):c.4437-7A>G

gnomAD frequency: 0.00003  dbSNP: rs370354306

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001703689	SCV000522031	likely benign	not provided	2020-01-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28779002)
Invitae	RCV000472403	SCV000558359	likely benign	Ataxia-telangiectasia syndrome	2023-12-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579570	SCV000682207	likely benign	Hereditary cancer-predisposing syndrome	2015-07-20	criteria provided, single submitter	clinical testing
Counsyl	RCV000472403	SCV000798693	uncertain significance	Ataxia-telangiectasia syndrome	2018-03-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000423984	SCV000918557	uncertain significance	not specified	2018-08-31	criteria provided, single submitter	clinical testing	Variant summary: ATM c.4437-7A>G 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. The variant allele was found at a frequency of 2.8e-05 in 245686 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4437-7A>G has been reported in the literature in individuals affected with Breast Cancer. This report does 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. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3 likely benign, 1 VUS). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003959898	SCV004776229	likely benign	ATM-related condition	2020-04-03	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).