dbSNP rs12693968: BMPR2:c.77-26905G>A (chr2-202437904-G-A) – 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.77-26905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 150,068 control chromosomes in the GnomAD database, including 8,653 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 0.31 ( 8653 hom., cov: 32)

Consequence

BMPR2
NM_001204.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.401

Publications

5 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.77-26905G>A		intron_variant	Intron 1 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2 link	c.77-26905G>A		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.77-26905G>A		intron_variant	Intron 1 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2 link	c.77-26905G>A		intron_variant	Intron 1 of 11	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46098

AN:

149950

Hom.:

8628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.283

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

GnomAD4 genome

AF:

0.308

AC:

46161

AN:

150068

Hom.:

8653

Cov.:

AF XY:

0.309

AC XY:

22657

AN XY:

73350

show subpopulations

African (AFR)

AF:

0.428

AC:

16950

AN:

39590

American (AMR)

AF:

0.305

AC:

4635

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

524

AN:

3464

East Asian (EAS)

AF:

0.120

AC:

622

AN:

5184

South Asian (SAS)

AF:

0.369

AC:

1780

AN:

4820

European-Finnish (FIN)

AF:

0.307

AC:

3239

AN:

10534

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.259

AC:

17607

AN:

67982

Other (OTH)

AF:

0.281

AC:

589

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1517

3033

4550

6066

7583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.295

Hom.:

846

Bravo

AF:

0.312

Asia WGS

AF:

0.268

AC:

929

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.15

(source)

DANN

Benign

0.74

PhyloP100

-0.40

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