NM_001204.7:c.76+4067T>A

Variant names:

• chr2-202381617-T-A
• rs1980153
• NM_001204.7:c.76+4067T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 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+4067T>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+4067T>A		intron	N/A	ENSP00000363708.4
	BMPR2	ENST00000374574.2	TSL:2	c.76+4067T>A		intron	N/A	ENSP00000363702.2

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

African (AFR) AF: 0.0259 AC: 1077 AN: 41572

American (AMR) AF: 0.0976 AC: 1492 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0267 AC: 129 AN: 4828

European-Finnish (FIN) AF: 0.0851 AC: 903 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6868 AN: 68024

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		0.59
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: rs1980153; hg19: chr2-203246340;