dbSNP rs13426118: BMPR2:c.76+13212A>C (chr2-202390762-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001204.7(BMPR2):c.76+13212A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,994 control chromosomes in the GnomAD database, including 4,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 4230 hom., cov: 31)

Consequence

BMPR2
NM_001204.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.76+13212A>C		intron_variant	Intron 1 of 12	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.76+13212A>C		intron_variant	Intron 1 of 12		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10 link	c.76+13212A>C		intron_variant	Intron 1 of 12	1	NM_001204.7	ENSP00000363708.4		Q13873-1
BMPR2	ENST00000374574.2 link	c.76+13212A>C		intron_variant	Intron 1 of 11	2		ENSP00000363702.2		Q13873-2

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31054

AN:

151876

Hom.:

4220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0821

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.205

AC:

31093

AN:

151994

Hom.:

4230

Cov.:

AF XY:

0.204

AC XY:

15127

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.389

AC:

16129

AN:

41432

American (AMR)

AF:

0.177

AC:

2704

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0821

AC:

285

AN:

3472

East Asian (EAS)

AF:

0.117

AC:

605

AN:

5168

South Asian (SAS)

AF:

0.248

AC:

1196

AN:

4820

European-Finnish (FIN)

AF:

0.117

AC:

1239

AN:

10560

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8381

AN:

67972

Other (OTH)

AF:

0.202

AC:

426

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1157

2314

3471

4628

5785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.140

Hom.:

2064

Bravo

AF:

0.217

Asia WGS

AF:

0.225

AC:

783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

(source)

DANN

Benign

0.80

PhyloP100

0.13

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over