rs6751210

Variant names:

• chr2-202488214-A-G
• rs6751210
• NM_001204.7:c.418+20525A>G

Variant summary

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

The NM_001204.7(BMPR2):​c.418+20525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,974 control chromosomes in the GnomAD database, including 20,085 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 0.51 (20085 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.418+20525A>G		intron_variant	Intron 3 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.418+20525A>G		intron_variant	Intron 3 of 12		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.418+20525A>G		intron_variant	Intron 3 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.418+20525A>G		intron_variant	Intron 3 of 11	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76903 AN: 151856 Hom.: 20053 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.507 AC: 76987 AN: 151974 Hom.: 20085 Cov.: 31 AF XY: 0.502 AC XY: 37285 AN XY: 74272

African (AFR) AF: 0.614 AC: 25432 AN: 41426

American (AMR) AF: 0.486 AC: 7429 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3466

East Asian (EAS) AF: 0.202 AC: 1047 AN: 5176

South Asian (SAS) AF: 0.506 AC: 2433 AN: 4810

European-Finnish (FIN) AF: 0.449 AC: 4729 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32894 AN: 67960

Other (OTH) AF: 0.517 AC: 1090 AN: 2108

Alfa AF: 0.492 Hom.: 30733

Bravo AF: 0.514

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.27
PhyloP100		-0.079
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: rs6751210; hg19: chr2-203352937;