NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr) AND Primary pulmonary hypertension

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 19, 2023
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:: RCV003595881.2

Allele description [Variation Report for NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)]

NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.2

Genomic location:

Preferred name:

NM_001204.7(BMPR2):c.797G>C (p.Arg266Thr)

Other names:

p.R266T:AGA>ACA; NM_001204.7(BMPR2):c.797G>C; p.Arg266Thr

HGVS:

NC_000002.12:g.202518997G>C
NG_009363.1:g.147671G>C
NM_001204.7:c.797G>CMANE SELECT
NP_001195.2:p.Arg266Thr
LRG_712t1:c.797G>C
LRG_712:g.147671G>C
LRG_712p1:p.R266T
NC_000002.11:g.203383720G>C
NM_001204.6:c.797G>C
NP_001195.2:p.R266T

Protein change:

R266T

Links:

dbSNP: rs374694591

NCBI 1000 Genomes Browser:

rs374694591

Molecular consequence:

NM_001204.7:c.797G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

BJ043209 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clon...
BJ043209 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clone XL034c09 5', mRNA sequence
gi|17415106|gnl|dbEST|10501380|dbj| 209.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004313171	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16429395, 31727138, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004313171

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 19, 2023)

germline

clinical testing

PubMed (3)
[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

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

Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension.

Zhu N, Pauciulo MW, Welch CL, Lutz KA, Coleman AW, Gonzaga-Jauregui C, Wang J, Grimes JM, Martin LJ, He H; PAH Biobank Enrolling Centers’ Investigators., Shen Y, Chung WK, Nichols WC.

Genome Med. 2019 Nov 14;11(1):69. doi: 10.1186/s13073-019-0685-z. Erratum in: Genome Med. 2022 Feb 7;14(1):12. doi: 10.1186/s13073-022-01014-0.

PubMed [citation]

PMID:: 31727138
PMCID:: PMC6857288

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004313171.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 266 of the BMPR2 protein (p.Arg266Thr). This variant is present in population databases (rs374694591, gnomAD 0.01%). This missense change has been observed in individual(s) with idiopathic pulmonary arterial hypertension and/or pulmonary arterial hypertension associated with other medical conditions (PMID: 16429395, 31727138). ClinVar contains an entry for this variant (Variation ID: 212810). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 26, 2024

ClinVar

Relating variation to medicine