NM_001204.7:c.77-32464T>G

Variant names:

• chr2-202432345-T-G
• rs13010656
• NM_001204.7:c.77-32464T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204.7(BMPR2):​c.77-32464T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 150,198 control chromosomes in the GnomAD database, including 19,183 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 0.49 (19183 hom., cov: 32)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7	c.77-32464T>G		intron_variant	Intron 1 of 12	ENST00000374580.10	NP_001195.2
BMPR2	XM_011511687.2	c.77-32464T>G		intron_variant	Intron 1 of 12		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10	c.77-32464T>G		intron_variant	Intron 1 of 12	1	NM_001204.7	ENSP00000363708.4
BMPR2	ENST00000374574.2	c.77-32464T>G		intron_variant	Intron 1 of 11	2		ENSP00000363702.2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 72980 AN: 150078 Hom.: 19151 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.486 AC: 73063 AN: 150198 Hom.: 19183 Cov.: 32 AF XY: 0.481 AC XY: 35304 AN XY: 73398

African (AFR) AF: 0.557 AC: 22121 AN: 39696

American (AMR) AF: 0.478 AC: 7273 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3472

East Asian (EAS) AF: 0.175 AC: 905 AN: 5184

South Asian (SAS) AF: 0.461 AC: 2224 AN: 4822

European-Finnish (FIN) AF: 0.447 AC: 4721 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32837 AN: 67960

Other (OTH) AF: 0.502 AC: 1054 AN: 2098

Alfa AF: 0.491 Hom.: 2540

Bravo AF: 0.494

Asia WGS AF: 0.357 AC: 1234 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.53
PhyloP100		-2.3
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: rs13010656; hg19: chr2-203297068;