Submissions for variant NM_000051.4(ATM):c.6147T>C (p.Tyr2049=)

gnomAD frequency: 0.00011  dbSNP: rs369940136

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000167192	SCV000218029	likely benign	Hereditary cancer-predisposing syndrome	2014-12-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232472	SCV000283008	likely benign	Ataxia-telangiectasia syndrome	2023-11-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000167192	SCV001351125	likely benign	Hereditary cancer-predisposing syndrome	2015-12-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193035	SCV001361580	likely benign	not specified	2019-08-26	criteria provided, single submitter	clinical testing	Variant summary: ATM c.6147T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 3.6e-05 in 251406 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.6147T>C in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx	RCV001610476	SCV001842253	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589820	SCV005084676	benign	Familial cancer of breast	2024-06-03	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.