2-202529625-G-T

Variant names:

• chr2-202529625-G-T
• rs12467409
• NM_001204.7:c.968-1169G>T

Variant summary

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

The NM_001204.7(BMPR2):​c.968-1169G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,198 control chromosomes in the GnomAD database, including 970 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 0.098 (970 hom., cov: 33)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	NM_001204.7	MANE Select	c.968-1169G>T		intron	N/A	NP_001195.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR2	ENST00000374580.10	TSL:1 MANE Select	c.968-1169G>T		intron	N/A	ENSP00000363708.4	Q13873-1
	BMPR2	ENST00000374574.2	TSL:2	c.968-1169G>T		intron	N/A	ENSP00000363702.2	Q13873-2

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14915 AN: 152080 Hom.: 971 Cov.: 33

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.0979 AC: 14904 AN: 152198 Hom.: 970 Cov.: 33 AF XY: 0.101 AC XY: 7487 AN XY: 74386

African (AFR) AF: 0.0226 AC: 937 AN: 41552

American (AMR) AF: 0.135 AC: 2062 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.117 AC: 608 AN: 5186

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4828

European-Finnish (FIN) AF: 0.116 AC: 1232 AN: 10580

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8260 AN: 67990

Other (OTH) AF: 0.124 AC: 261 AN: 2110

Alfa AF: 0.0708 Hom.: 92

Bravo AF: 0.0938

Asia WGS AF: 0.197 AC: 684 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.66
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12467409; hg19: chr2-203394348;