rs1061157

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001204.7(BMPR2):c.2811G>A(p.Arg937Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,998 control chromosomes in the GnomAD database, including 12,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 883 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11740 hom. )

Consequence

BMPR2
NM_001204.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.44

Publications

28 publications found

Variant links:

Genes affected

BMPR2 (HGNC:1078): (bone morphogenetic protein receptor type 2) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease. [provided by RefSeq, May 2020]

BMPR2 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
pulmonary hypertension, primary, 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
heritable pulmonary arterial hypertension
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

BMPR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-202556476-G-A is Benign according to our data. Variant chr2-202556476-G-A is described in ClinVar as [Benign]. Clinvar id is 136529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.2811G>A	p.Arg937Arg	synonymous_variant	Exon 12 of 13	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.2811G>A	p.Arg937Arg	synonymous_variant	Exon 12 of 13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10 link	c.2811G>A	p.Arg937Arg	synonymous_variant	Exon 12 of 13	1	NM_001204.7	ENSP00000363708.4		Q13873-1
BMPR2	ENST00000374574.2 link	c.1587-3220G>A		intron_variant	Intron 11 of 11	2		ENSP00000363702.2		Q13873-2

Frequencies

GnomAD3 genomes

AF:

0.0934

AC:

14207

AN:

152100

Hom.:

883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.0870

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0690

Gnomad EAS

AF:

0.0966

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.119

AC:

29883

AN:

251166

AF XY:

0.127

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.0829

Gnomad ASJ exome

AF:

0.0751

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.120

AC:

175695

AN:

1461780

Hom.:

11740

Cov.:

AF XY:

0.124

AC XY:

90147

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0176

AC:

588

AN:

33480

American (AMR)

AF:

0.0842

AC:

3767

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0762

AC:

1991

AN:

26136

East Asian (EAS)

AF:

0.0754

AC:

2994

AN:

39700

South Asian (SAS)

AF:

0.234

AC:

20197

AN:

86254

European-Finnish (FIN)

AF:

0.123

AC:

6582

AN:

53338

Middle Eastern (MID)

AF:

0.116

AC:

670

AN:

5768

European-Non Finnish (NFE)

AF:

0.118

AC:

131561

AN:

1111986

Other (OTH)

AF:

0.122

AC:

7345

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

9934

19868

29801

39735

49669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0933

AC:

14196

AN:

152218

Hom.:

883

Cov.:

AF XY:

0.0959

AC XY:

7138

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0211

AC:

876

AN:

41568

American (AMR)

AF:

0.108

AC:

1658

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0690

AC:

239

AN:

3462

East Asian (EAS)

AF:

0.0964

AC:

500

AN:

5186

South Asian (SAS)

AF:

0.243

AC:

1169

AN:

4820

European-Finnish (FIN)

AF:

0.116

AC:

1226

AN:

10584

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8162

AN:

68004

Other (OTH)

AF:

0.115

AC:

242

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

644

1288

1931

2575

3219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.106

Hom.:

1515

Bravo

AF:

0.0852

Asia WGS

AF:

0.186

AC:

644

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 06, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg937Arg in exon 12 of BMPR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 12.6% (1085/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1061157). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 13, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary pulmonary hypertension

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pulmonary hypertension, primary, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.8

(source)

DANN

Benign

0.55

PhyloP100

1.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1061157

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over