Submissions for variant NM_004329.3(BMPR1A):c.1296C>T (p.Ser432=)

gnomAD frequency: 0.00001  dbSNP: rs1060504907

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476025	SCV000562756	likely benign	Juvenile polyposis syndrome	2024-01-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001696912	SCV000724979	likely benign	not provided	2019-03-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000772723	SCV000906016	likely benign	Hereditary cancer-predisposing syndrome	2018-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000772723	SCV001171062	likely benign	Hereditary cancer-predisposing syndrome	2015-09-18	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.
All of Us Research Program, National Institutes of Health	RCV000476025	SCV004835998	likely benign	Juvenile polyposis syndrome	2023-06-26	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354942	SCV001549674	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The BMPR1A p.Ser432Ser variant was not identified in the literature nor was it identified in the dbSNP or LOVD 3.0 databases. The variant was identified in ClinVar (classified as likely benign by Invitae and GeneDx). The variant was identified in control databases in 2 of 277246 chromosomes at a frequency of 0.000007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 2 of 126732 chromosomes (freq: 0.000016), but not in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish or South Asian populations. The p.Ser432Ser variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.