Submissions for variant NM_001204.7(BMPR2):c.296G>A (p.Cys99Tyr)

dbSNP: rs1085307205

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001376614	SCV001410158	pathogenic	Primary pulmonary hypertension	2019-07-11	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys99 amino acid residue in BMPR2. Other variant(s) that disrupt this residue have been observed in individuals with BMPR2-related conditions (PMID: 19555857, 29631995), which suggests that this may be a clinically significant amino acid residue. This variant has been observed in individuals affected with pulmonary artery hypertension (PMID: 19555857, 30578397, Invitae). ClinVar contains an entry for this variant (Variation ID: 425754). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 99 of the BMPR2 protein (p.Cys99Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine.
Rare Disease Genomics Group, St George's University of London	RCV000488629	SCV000576030	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only