Variant rs1553503208 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_001204.7(BMPR2):c.211G>A(p.Glu71Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BMPR2
NM_001204.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.26

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:

BMPR2 (HGNC:):

BMPR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BMPR2. . Gene score misZ 2.0624 (greater than the threshold 3.09). Trascript score misZ 3.2701 (greater than threshold 3.09). GenCC has associacion of gene with pulmonary hypertension, primary, 1, congenital heart disease, heritable pulmonary arterial hypertension, pulmonary arterial hypertension.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7 linkuse as main transcript	c.211G>A	p.Glu71Lys	missense_variant	2/13	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 linkuse as main transcript	c.211G>A	p.Glu71Lys	missense_variant	2/13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BMPR2	ENST00000374580.10 linkuse as main transcript	c.211G>A	p.Glu71Lys	missense_variant	2/13	1	NM_001204.7	ENSP00000363708.4	Q13873-1
BMPR2	ENST00000374574.2 linkuse as main transcript	c.211G>A	p.Glu71Lys	missense_variant	2/12	2		ENSP00000363702.2	Q13873-2
BMPR2	ENST00000479069.1 linkuse as main transcript	n.118G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pulmonary arterial hypertension associated with congenital heart disease

Uncertain:1

Uncertain significance, criteria provided, single submitter

case-control

Wendy Chung Laboratory, Columbia University Medical Center

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

D;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Benign

0.98

L;L;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.77

N;N;.

REVEL

Pathogenic

0.75

Sift

Benign

0.14

T;T;.

Sift4G

Benign

0.55

T;T;.

Polyphen

0.73

P;.;.

Vest4

0.86

MutPred

0.66

Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);.;

MVP

0.97

MPC

1.1

ClinPred

0.93

GERP RS

5.5

Varity_R

0.66

gMVP

0.68

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