rs4675278

Variant names:

• chr2-202469849-A-G
• rs4675278
• NM_001204.7:c.418+2160A>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+2160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 150,240 control chromosomes in the GnomAD database, including 31,696 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 0.64 (31696 hom., cov: 29)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.418+2160A>G		intron_variant	Intron 3 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.418+2160A>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+2160A>G		intron_variant	Intron 3 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.418+2160A>G		intron_variant	Intron 3 of 11	2		ENSP00000363702.2
BMPR2	ENST00000479069.1	n.325+2160A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 96489 AN: 150130 Hom.: 31672 Cov.: 29

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.643 AC: 96557 AN: 150240 Hom.: 31696 Cov.: 29 AF XY: 0.636 AC XY: 46695 AN XY: 73388

African (AFR) AF: 0.565 AC: 22767 AN: 40302

American (AMR) AF: 0.645 AC: 9723 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1036 AN: 5110

South Asian (SAS) AF: 0.589 AC: 2815 AN: 4776

European-Finnish (FIN) AF: 0.706 AC: 7376 AN: 10452

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48723 AN: 67782

Other (OTH) AF: 0.657 AC: 1362 AN: 2074

Alfa AF: 0.699 Hom.: 43429

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.069
PhyloP100		-0.91
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: rs4675278; hg19: chr2-203334572;