Submissions for variant NM_001204.7(BMPR2):c.2695C>T (p.Arg899Ter)

dbSNP: rs137852741

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001376577	SCV000754706	pathogenic	Primary pulmonary hypertension	2023-03-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg899*) in the BMPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BMPR2 are known to be pathogenic (PMID: 16429395). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with pulmonary hypertension (PMID: 10973254, 11115378, 15146475, 19555857, 21737554, 21801371, 23592887). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 8796). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000763065	SCV000893568	pathogenic	Pulmonary hypertension, primary, 1; Pulmonary venoocclusive disease 1	2018-10-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001810839	SCV001472155	pathogenic	not provided	2019-12-16	criteria provided, single submitter	clinical testing	The BMPR2 c.2695C>T; p.Arg899Ter variant (rs137852741) is reported in the literature in multiple individuals affected with PAH (International PPH Consortium 2000, Machado 2009). This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: International PPH Consortium. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet. 2000 Sep;26(1):81-4. Machado RD et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S32-42.
OMIM	RCV000009341	SCV000029559	pathogenic	Pulmonary hypertension, primary, 1	2000-09-01	no assertion criteria provided	literature only
Rare Disease Genomics Group, St George's University of London	RCV000009341	SCV000576306	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003746	SCV001162189	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823864	SCV002073559	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only