rs17199235

Positions:

• chr2-202555136-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001204.7(BMPR2):​c.1587-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 930,674 control chromosomes in the GnomAD database, including 5,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (679 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4751 hom.)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-202555136-A-G is Benign according to our data. Variant chr2-202555136-A-G is described in ClinVar as [Benign]. Clinvar id is 676056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.1587-116A>G		intron_variant		ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.1587-116A>G		intron_variant			XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.1587-116A>G		intron_variant		1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.1586+2248A>G		intron_variant		2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12084 AN: 152168 Hom.: 678 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.102 AC: 79355 AN: 778388 Hom.: 4751 AF XY: 0.101 AC XY: 40742 AN XY: 405238

Gnomad4 AFR exome AF: 0.0172

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.000179

Gnomad4 SAS exome AF: 0.0545

Gnomad4 FIN exome AF: 0.0872

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0794 AC: 12084 AN: 152286 Hom.: 679 Cov.: 32 AF XY: 0.0763 AC XY: 5681 AN XY: 74464

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.111 Hom.: 1359

Bravo AF: 0.0762

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.30

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: rs17199235; hg19: chr2-203419859;