rs16839127

Variant names:

• chr2-202401887-G-A
• rs16839127
• NM_001204.7:c.76+24337G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001204.7(BMPR2):​c.76+24337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 152,302 control chromosomes in the GnomAD database, including 296 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 0.054 (296 hom., cov: 32)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	NM_001204.7	MANE Select	c.76+24337G>A		intron	N/A	NP_001195.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	ENST00000374580.10	TSL:1 MANE Select	c.76+24337G>A		intron	N/A	ENSP00000363708.4
	BMPR2	ENST00000374574.2	TSL:2	c.76+24337G>A		intron	N/A	ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8290 AN: 152184 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.00904

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0544 AC: 8287 AN: 152302 Hom.: 296 Cov.: 32 AF XY: 0.0515 AC XY: 3838 AN XY: 74478

African (AFR) AF: 0.0359 AC: 1491 AN: 41570

American (AMR) AF: 0.0614 AC: 940 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 313 AN: 3470

East Asian (EAS) AF: 0.00925 AC: 48 AN: 5188

South Asian (SAS) AF: 0.0595 AC: 287 AN: 4822

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10624

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0682 AC: 4637 AN: 68010

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.0635 Hom.: 168

Bravo AF: 0.0582

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		-0.13
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: rs16839127; hg19: chr2-203266610;