NM_001204.7(BMPR2):c.2291dup (p.Asn764fs) AND Primary pulmonary hypertension

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 11, 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:: RCV003596002.2

Allele description [Variation Report for NM_001204.7(BMPR2):c.2291dup (p.Asn764fs)]

NM_001204.7(BMPR2):c.2291dup (p.Asn764fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2q33.2

Genomic location:

Preferred name:

NM_001204.7(BMPR2):c.2291dup (p.Asn764fs)

HGVS:

NC_000002.12:g.202555956dup
NG_009363.1:g.184630dup
NM_001204.7:c.2291dupMANE SELECT
NP_001195.2:p.Asn764fs
LRG_712t1:c.2291dup
LRG_712:g.184630dup
LRG_712p1:p.N764Kfs*49
NC_000002.11:g.203420674_203420675insA
NC_000002.11:g.203420679dup
NM_001204.6:c.2291dupA
NP_001195.2:p.N764Kfs*49

Protein change:

N764fs

Links:

dbSNP: rs1085307377

NCBI 1000 Genomes Browser:

rs1085307377

Molecular consequence:

NM_001204.7:c.2291dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004293053	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 11, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16429395, 11115378, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293053

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 11, 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

BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension.

Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galiè N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE, Trembath RC, et al.

Am J Hum Genet. 2001 Jan;68(1):92-102. Epub 2000 Dec 12.

PubMed [citation]

PMID:: 11115378
PMCID:: PMC1234937

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293053.1

#	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 creates a premature translational stop signal (p.Asn764Lysfs*49) in the BMPR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BMPR2 are known to be pathogenic (PMID: 16429395). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with pulmonary hypertension (PMID: 11115378). This variant is also known as 2292insA (N764fs). ClinVar contains an entry for this variant (Variation ID: 425977). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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