rs13430786

Variant names:

• chr2-202444343-G-A
• rs13430786
• NM_001204.7:c.77-20466G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-202444343-G-A
• chr2-202444343-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204.7(BMPR2):​c.77-20466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 150,096 control chromosomes in the GnomAD database, including 8,570 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 (8570 hom., cov: 32)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.77-20466G>A		intron_variant	Intron 1 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.77-20466G>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	c.77-20466G>A		intron_variant	Intron 1 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.77-20466G>A		intron_variant	Intron 1 of 11	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 45820 AN: 149976 Hom.: 8548 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.359

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: 0.306 AC: 45884 AN: 150096 Hom.: 8570 Cov.: 32 AF XY: 0.307 AC XY: 22526 AN XY: 73380

African (AFR) AF: 0.426 AC: 16884 AN: 39648

American (AMR) AF: 0.303 AC: 4606 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3466

East Asian (EAS) AF: 0.100 AC: 519 AN: 5178

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4822

European-Finnish (FIN) AF: 0.307 AC: 3237 AN: 10548

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17579 AN: 67954

Other (OTH) AF: 0.281 AC: 588 AN: 2094

Alfa AF: 0.240 Hom.: 1812

Bravo AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-1.6
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: rs13430786; hg19: chr2-203309066;