Submissions for variant NM_004329.3(BMPR1A):c.117C>G (p.Ser39=)

dbSNP: rs757333646

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234488	SCV000288381	likely benign	Juvenile polyposis syndrome	2024-10-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001705262	SCV000534255	likely benign	not provided	2018-11-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000574615	SCV000668300	likely benign	Hereditary cancer-predisposing syndrome	2015-05-14	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.
Color Diagnostics, LLC DBA Color Health	RCV000574615	SCV000682843	likely benign	Hereditary cancer-predisposing syndrome	2016-06-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000436146	SCV000916694	likely benign	not specified	2018-04-13	criteria provided, single submitter	clinical testing	Variant summary: BMPR1A c.117C>G 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 1.6e-05 (4/246138 control chromosomes). This frequency is approximately 8 fold above the estimated maximal expected allele frequency for a pathogenic variant in BMPR1A causing Juvenile Polyposis Syndrome phenotype (2e-06), suggesting that the variant is benign. To our knowledge, no occurrence of c.117C>G in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
All of Us Research Program, National Institutes of Health	RCV000234488	SCV004840689	likely benign	Juvenile polyposis syndrome	2023-12-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000234488	SCV005404047	benign	Juvenile polyposis syndrome	2024-07-31	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.