rs17199235

Variant names:

• chr2-202555136-A-G
• rs17199235
• NM_001204.7:c.1587-116A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001204.7(BMPR2):​c.1587-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 930,674 control chromosomes in the GnomAD database, including 5,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). The gene BMPR2 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.079 (679 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4751 hom.)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334
• Publications: 6 publications found

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

ACMG classification

Specifications for BMPR2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-202555136-A-G is Benign according to our data. Variant chr2-202555136-A-G is described in ClinVar as Benign. ClinVar VariationId is 676056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	NM_001204.7	MANE Select	c.1587-116A>G		intron	N/A	NP_001195.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	ENST00000374580.10	TSL:1 MANE Select	c.1587-116A>G		intron	N/A	ENSP00000363708.4	Q13873-1
	BMPR2	ENST00000374574.2	TSL:2	c.1586+2248A>G		intron	N/A	ENSP00000363702.2	Q13873-2

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12084 AN: 152168 Hom.: 678 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.102 AC: 79355 AN: 778388 Hom.: 4751 AF XY: 0.101 AC XY: 40742 AN XY: 405238

African (AFR) AF: 0.0172 AC: 328 AN: 19118

American (AMR) AF: 0.0547 AC: 1647 AN: 30116

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 3969 AN: 20308

East Asian (EAS) AF: 0.000179 AC: 6 AN: 33452

South Asian (SAS) AF: 0.0545 AC: 3392 AN: 62220

European-Finnish (FIN) AF: 0.0872 AC: 3194 AN: 36640

Middle Eastern (MID) AF: 0.116 AC: 409 AN: 3524

European-Non Finnish (NFE) AF: 0.117 AC: 62559 AN: 535394

Other (OTH) AF: 0.102 AC: 3851 AN: 37616

GnomAD4 genome AF: 0.0794 AC: 12084 AN: 152286 Hom.: 679 Cov.: 32 AF XY: 0.0763 AC XY: 5681 AN XY: 74464

African (AFR) AF: 0.0202 AC: 842 AN: 41584

American (AMR) AF: 0.0665 AC: 1017 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4826

European-Finnish (FIN) AF: 0.0808 AC: 857 AN: 10602

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8132 AN: 68010

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.111 Hom.: 1586

Bravo AF: 0.0762

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.30
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17199235; hg19: chr2-203419859;