NM_001204.7(BMPR2):c.295T>C (p.Cys99Arg) AND Primary pulmonary hypertension

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 21, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003595882.2

Allele description [Variation Report for NM_001204.7(BMPR2):c.295T>C (p.Cys99Arg)]

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

Gene:

BMPR2:bone morphogenetic protein receptor type 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

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

Other names:

p.C99R:TGT>CGT

HGVS:

NC_000002.12:g.202467566T>C
NG_009363.1:g.96240T>C
NM_001204.7:c.295T>CMANE SELECT
NP_001195.2:p.Cys99Arg
LRG_712t1:c.295T>C
LRG_712:g.96240T>C
LRG_712p1:p.C99R
NC_000002.11:g.203332289T>C
NM_001204.6:c.295T>C
NP_001195.2:p.C99R

Protein change:

C99R

Links:

dbSNP: rs863223425

NCBI 1000 Genomes Browser:

rs863223425

Molecular consequence:

NM_001204.7:c.295T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary pulmonary hypertension (PPH1)
Identifiers:: MONDO: MONDO:0001999; MedGen: C0152171

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293045	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 21, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30578397, 16429395, 19555857, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293045

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 21, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension.

Wang XJ, Lian TY, Jiang X, Liu SF, Li SQ, Jiang R, Wu WH, Ye J, Cheng CY, Du Y, Xu XQ, Wu Y, Peng FH, Sun K, Mao YM, Yu H, Liang C, Shyy JY, Zhang SY, Zhang X, Jing ZC.

Eur Respir J. 2019 Mar 14;53(3). doi:pii: 1801609. 10.1183/13993003.01609-2018. Print 2019 Mar.

PubMed [citation]

PMID:: 30578397

Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension.

Machado RD, Aldred MA, James V, Harrison RE, Patel B, Schwalbe EC, Gruenig E, Janssen B, Koehler R, Seeger W, Eickelberg O, Olschewski H, Elliott CG, Glissmeyer E, Carlquist J, Kim M, Torbicki A, Fijalkowska A, Szewczyk G, Parma J, Abramowicz MJ, Galie N, et al.

Hum Mutat. 2006 Feb;27(2):121-32.

PubMed [citation]

PMID:: 16429395

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293045.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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