Submissions for variant NM_001204.7(BMPR2):c.439C>T (p.Arg147Ter)

dbSNP: rs869025366

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000208112	SCV000263791	pathogenic	Pulmonary hypertension, primary, 1	2015-04-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000489453	SCV000577634	pathogenic	not provided	2020-04-28	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in ClinVar as pathogenic (ClinVar Variant ID# 222513; Landrum et al., 2016); Other nonsense variants have been reported in the Human Gene Mutation Database in individuals with PAH (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 26387786, 32581362, 20534176, 14526373, 16717148, 20002458, 16429395, 15146475, 25612240, 25525159, 21801371, 21737554, 11115378, 29743074, 29023671, 30578397, 18356561, 31727138)
Invitae	RCV001376625	SCV001410770	pathogenic	Primary pulmonary hypertension	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg147*) 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 present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with pulmonary hypertension (PMID: 11115378, 15146475, 16717148, 18503968, 30578397). ClinVar contains an entry for this variant (Variation ID: 222513). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002500667	SCV002810345	pathogenic	Pulmonary hypertension, primary, 1; Pulmonary venoocclusive disease 1	2022-05-01	criteria provided, single submitter	clinical testing
Rare Disease Genomics Group, St George's University of London	RCV000208112	SCV000576071	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003673	SCV001162116	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823881	SCV002073586	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only