rs4675278

Positions:

• chr2-202469849-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.418+2160A>G		intron_variant		ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.418+2160A>G		intron_variant			XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.418+2160A>G		intron_variant		1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.418+2160A>G		intron_variant		2		ENSP00000363702.2
BMPR2	ENST00000479069.1	n.325+2160A>G		intron_variant		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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.657

Alfa AF: 0.701 Hom.: 35628

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4675278; hg19: chr2-203334572;