ClinVar Miner

Submissions for variant NM_001204.7(BMPR2):c.631C>T (p.Arg211Ter) (rs137852753)

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Total submissions: 8
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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.
Invitae RCV000009357 SCV000629982 pathogenic Primary pulmonary hypertension 2017-03-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 211 (p.Arg211*) of 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. This particular variant has been reported in the literature in several individuals with pulmonary arterial hypertension (PMID: 11015450, 19555857, 20534176). ClinVar contains an entry for this variant (Variation ID: 8812). For these reasons, this variant has been classified as Pathogenic.
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.
OMIM RCV000009357 SCV000029575 pathogenic Primary pulmonary hypertension 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
Medical & Molecular Genetics Group,University of Lincoln RCV000009357 SCV000576091 pathogenic Primary pulmonary hypertension no assertion criteria provided literature only
Medical & Molecular Genetics Group,University of Lincoln 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

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