Submissions for variant NM_001204.7(BMPR2):c.200A>G (p.Tyr67Cys)

dbSNP: rs1085307177

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383602	SCV001582803	pathogenic	Primary pulmonary hypertension	2023-10-06	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 67 of the BMPR2 protein (p.Tyr67Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with pulmonary arterial hypertension (PMID: 15146475, 16429395, 18356561, 20002458). ClinVar contains an entry for this variant (Variation ID: 425719). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BMPR2 protein function. Experimental studies have shown that this missense change affects BMPR2 function (PMID: 25187962). For these reasons, this variant has been classified as Pathogenic.
Rare Disease Genomics Group, St George's University of London	RCV000488664	SCV000575993	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003651	SCV001162094	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823909	SCV002073564	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only