Submissions for variant NM_001204.7(BMPR2):c.631C>T (p.Arg211Ter)

dbSNP: rs137852753

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197776	SCV000249640	pathogenic	not provided	2017-02-07	criteria provided, single submitter	clinical testing	The R211X variant in the BMPR2 gene has been reported in individuals with familial PAH as well as in families with sporadic idopathic PAH, and was absent from greater than 260 control chromosomes (Cogen et al., 2006; Elliot et al., 2006; Humbert et al, 2002; Machado et al., 2001; Machado et al., 2009; Pfarr et al., 2011; Portillo et al, 2010; Thompson et al., 2000). R211X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the BMPR2 gene have been reported in association with PAH. In summary, R211X in the BMPR2 gene is interpreted as a disease-causing variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002228023	SCV000629982	pathogenic	Primary pulmonary hypertension	2023-01-24	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 8812). This premature translational stop signal has been observed in individual(s) with pulmonary arterial hypertension (PMID: 11015450, 19555857, 20534176). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg211*) 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).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000197776	SCV000885066	pathogenic	not provided	2018-04-11	criteria provided, single submitter	clinical testing	The BMPR2 c.631C>T; p.Arg211Ter variant (rs137852753) has been described in several individuals affected with familial and sporadic pulmonary hypertension (Humbert 2002, Machado 2001, Machado 2006, Portillo 2010, Sztrymf 2008, Thomson 2000). It has been reported as pathogenic by several laboratories in ClinVar (Variation ID: 8812) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and 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 pathogenic. References: Humbert M et al. BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives. Eur Respir J. 2002 Sep;20(3):518-23. Machado R et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet. 2001 Jan;68(1):92-102. Machado R et al. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat. 2006 Feb;27(2):121-32. Portillo K et al. Study of the BMPR2 gene in patients with pulmonary arterial hypertension. Arch Bronconeumol. 2010 Mar;46(3):129-34. Sztrymf B et al. Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1377-83. Thomson J et al. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. J Med Genet. 2000 Oct;37(10):741-5.
Fulgent Genetics, Fulgent Genetics	RCV002476949	SCV002790298	pathogenic	Pulmonary hypertension, primary, 1; Pulmonary venoocclusive disease 1	2022-05-26	criteria provided, single submitter	clinical testing
OMIM	RCV000009357	SCV000029575	pathogenic	Pulmonary hypertension, primary, 1	2002-09-01	no assertion criteria provided	literature only
OMIM	RCV000009358	SCV000029576	pathogenic	Pulmonary hypertension, primary, dexfenfluramine-associated	2002-09-01	no assertion criteria provided	literature only
Rare Disease Genomics Group, St George's University of London	RCV000009357	SCV000576091	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
Rare Disease Genomics Group, St George's University of London	RCV000009358	SCV000576092	pathogenic	Pulmonary hypertension, primary, dexfenfluramine-associated		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003683	SCV001162126	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823871	SCV002073592	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only