rs1980153

chr2-202381617-T-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+4067T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 152,310 control chromosomes in the GnomAD database, including 528 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 0.073 (528 hom., cov: 31)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR2	NM_001204.7	c.76+4067T>A		intron_variant		ENST00000374580.10
BMPR2	XM_011511687.2	c.76+4067T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR2	ENST00000374580.10	c.76+4067T>A		intron_variant		1	NM_001204.7	P1
BMPR2	ENST00000374574.2	c.76+4067T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11142 AN: 152192 Hom.: 528 Cov.: 31

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0977

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0731 AC: 11134 AN: 152310 Hom.: 528 Cov.: 31 AF XY: 0.0702 AC XY: 5230 AN XY: 74484

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0267

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0342 Hom.: 17

Bravo AF: 0.0759

Asia WGS AF: 0.0160 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.6
Dann	Benign	0.73

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: rs1980153; hg19: chr2-203246340;