rs1061157

Positions:

chr2-202556476-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001204.7(BMPR2):c.2811G>A(p.Arg937=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr2-202556476-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7 linkuse as main transcript	c.2811G>A	p.Arg937=	synonymous_variant	12/13	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2 linkuse as main transcript	c.2811G>A	p.Arg937=	synonymous_variant	12/13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10 linkuse as main transcript	c.2811G>A	p.Arg937=	synonymous_variant	12/13	1	NM_001204.7	ENSP00000363708	P1	Q13873-1
BMPR2	ENST00000374574.2 linkuse as main transcript	c.1587-3220G>A		intron_variant		2		ENSP00000363702		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

GnomAD3 exomes

AF:

0.119

AC:

29883

AN:

251166

Hom.:

2163

AF XY:

0.127

AC XY:

17251

AN XY:

135762

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 SAS exome

AF:

0.240

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

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0842

Gnomad4 ASJ exome

AF:

0.0762

Gnomad4 EAS exome

AF:

0.0754

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.0933

AC:

14196

AN:

152218

Hom.:

883

Cov.:

AF XY:

0.0959

AC XY:

7138

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0690

Gnomad4 EAS

AF:

0.0964

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.109

Hom.:

1286

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2013	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary pulmonary hypertension

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Pulmonary hypertension, primary, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

DANN

Benign

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over