Submissions for variant NM_000051.4(ATM):c.4437-9C>T

gnomAD frequency: 0.00002  dbSNP: rs766003804

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000195466	SCV000254108	likely benign	Ataxia-telangiectasia syndrome	2023-11-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001722111	SCV000512161	likely benign	not provided	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000582132	SCV000687548	likely benign	Hereditary cancer-predisposing syndrome	2017-08-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000195466	SCV000798406	likely benign	Ataxia-telangiectasia syndrome	2018-03-09	criteria provided, single submitter	clinical testing
Mendelics	RCV000195466	SCV001138502	likely benign	Ataxia-telangiectasia syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000433234	SCV001338440	uncertain significance	not specified	2020-04-30	criteria provided, single submitter	clinical testing	Variant summary: ATM c.4437-9C>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 2.4e-05 in 248642 control chromosomes. 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.4437-9C>T 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. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS - possibly benign.
Genetic Services Laboratory, University of Chicago	RCV000433234	SCV002068671	likely benign	not specified	2019-02-27	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589865	SCV005083119	likely benign	Familial cancer of breast	2024-05-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000433234	SCV005090392	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553087	SCV004728129	likely benign	ATM-related disorder	2020-09-30	no assertion criteria provided	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).