Submissions for variant NM_004329.3(BMPR1A):c.682C>A (p.Arg228=)

gnomAD frequency: 0.00001  dbSNP: rs587782682

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163613	SCV000214180	likely benign	Hereditary cancer-predisposing syndrome	2015-02-06	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	RCV001082166	SCV000562765	likely benign	Juvenile polyposis syndrome	2025-01-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163613	SCV000682910	likely benign	Hereditary cancer-predisposing syndrome	2016-07-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588778	SCV000698321	benign	not provided	2017-07-06	criteria provided, single submitter	clinical testing	Variant summary: The BMPR1A c.682C>A (p.Arg228Arg) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5/119922 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000076 (5/65736). This frequency is about 38 times the estimated maximal expected allele frequency of a pathogenic BMPR1A variant (0.000002), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000605333	SCV000730483	benign	not specified	2015-09-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Sema4, Sema4	RCV000163613	SCV002531111	likely benign	Hereditary cancer-predisposing syndrome	2020-09-25	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588778	SCV004222534	likely benign	not provided	2023-03-08	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001082166	SCV004842880	likely benign	Juvenile polyposis syndrome	2023-12-13	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001082166	SCV005404073	benign	Juvenile polyposis syndrome	2024-08-05	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.
PreventionGenetics, part of Exact Sciences	RCV003895107	SCV004710199	likely benign	BMPR1A-related disorder	2020-11-13	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).