Submissions for variant NM_001204.7(BMPR2):c.295T>C (p.Cys99Arg)

gnomAD frequency: 0.00001  dbSNP: rs863223425

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196343	SCV000249648	uncertain significance	not provided	2024-10-01	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31727138, 16429395, 29631995, 19555857)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003595882	SCV004293045	pathogenic	Primary pulmonary hypertension	2022-12-21	criteria provided, single submitter	clinical testing	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) performed at Invitae indicates that this missense variant is expected to disrupt BMPR2 protein function. 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 determined to be pathogenic (PMID: 19555857, 30578397; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 212816). This missense change has been observed in individuals with pulmonary arterial hypertension (PMID: 16429395, 19555857; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 99 of the BMPR2 protein (p.Cys99Arg).
Rare Disease Genomics Group, St George's University of London	RCV000488549	SCV000576029	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823879	SCV002073576	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only