rs4303700

Positions:

• chr2-202381688-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204.7(BMPR2):​c.76+4138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,162 control chromosomes in the GnomAD database, including 2,404 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 0.16 (2404 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.76+4138G>A		intron_variant		ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.76+4138G>A		intron_variant			XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.76+4138G>A		intron_variant		1	NM_001204.7	ENSP00000363708	P1
BMPR2	ENST00000374574.2	c.76+4138G>A		intron_variant		2		ENSP00000363702

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24830 AN: 152044 Hom.: 2403 Cov.: 31

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.163 AC: 24835 AN: 152162 Hom.: 2404 Cov.: 31 AF XY: 0.158 AC XY: 11718 AN XY: 74384

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0556

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.208

Alfa AF: 0.221 Hom.: 8164

Bravo AF: 0.165

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.099
DANN	Benign	0.55

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: rs4303700; hg19: chr2-203246411;