Submissions for variant NM_005359.6(SMAD4):c.582A>G (p.Thr194=)

gnomAD frequency: 0.00012  dbSNP: rs145805120

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000587852	SCV000518440	likely benign	not provided	2021-05-27	criteria provided, single submitter	clinical testing
Invitae	RCV001086982	SCV000556158	likely benign	Juvenile polyposis syndrome	2024-01-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000437773	SCV000602197	likely benign	not specified	2017-05-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002311458	SCV000671985	likely benign	Familial thoracic aortic aneurysm and aortic dissection; Hereditary cancer-predisposing syndrome	2015-08-07	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.
Color Diagnostics, LLC DBA Color Health	RCV000566093	SCV000686546	likely benign	Hereditary cancer-predisposing syndrome	2016-12-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587852	SCV000698578	benign	not provided	2016-05-03	criteria provided, single submitter	clinical testing	Variant summary: The SMAD4 c.582A>G variant affects a non-conserved nucleotide, resulting in a synonymous change. Mutation Taster predicts a damaging outcome for this variant. This variant was found in 13/121412 control chromosomes at a frequency of 0.0001071, which is about 54 times the maximal expected frequency of a pathogenic SMAD4 allele (0.000002), suggesting this variant is benign. In addition, one clinical laboratory classified this variant as benign, and the variant was found to co-occur with a pathogenic PMS2 variant (c.2186_2187delTC) in one internal specimen. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000587852	SCV000806703	likely benign	not provided	2017-05-25	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000566093	SCV002538334	benign	Hereditary cancer-predisposing syndrome	2021-04-23	criteria provided, single submitter	curation