rs6717924

Variant names:

• chr2-202381581-G-A
• rs6717924
• NM_001204.7:c.76+4031G>A

Variant summary

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

The NM_001204.7(BMPR2):​c.76+4031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,210 control chromosomes in the GnomAD database, including 1,252 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 0.12 (1252 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.76+4031G>A		intron_variant	Intron 1 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.76+4031G>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.76+4031G>A		intron_variant	Intron 1 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.76+4031G>A		intron_variant	Intron 1 of 11	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18857 AN: 152092 Hom.: 1249 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.124 AC: 18883 AN: 152210 Hom.: 1252 Cov.: 31 AF XY: 0.125 AC XY: 9316 AN XY: 74412

African (AFR) AF: 0.109 AC: 4525 AN: 41532

American (AMR) AF: 0.137 AC: 2092 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5186

South Asian (SAS) AF: 0.112 AC: 539 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1987 AN: 10578

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9191 AN: 68020

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.123 Hom.: 494

Bravo AF: 0.118

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.53
PhyloP100		-0.51
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: rs6717924; hg19: chr2-203246304;