rs12477602

Variant names:

• chr2-202473522-G-A
• rs12477602
• NM_001204.7:c.418+5833G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-202473522-G-A
• chr2-202473522-G-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.418+5833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,138 control chromosomes in the GnomAD database, including 1,193 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. The gene BMPR2 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.12 (1193 hom., cov: 33)
• Consequence: BMPR2 NM_001204.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• 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

Specifications for BMPR2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 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.418+5833G>A		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.418+5833G>A		intron	N/A	ENSP00000363708.4	Q13873-1
	BMPR2	ENST00000374574.2	TSL:2	c.418+5833G>A		intron	N/A	ENSP00000363702.2	Q13873-2
	BMPR2	ENST00000479069.1	TSL:3	n.326-1186G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18084 AN: 152020 Hom.: 1190 Cov.: 33

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.119 AC: 18101 AN: 152138 Hom.: 1193 Cov.: 33 AF XY: 0.120 AC XY: 8951 AN XY: 74354

African (AFR) AF: 0.0907 AC: 3766 AN: 41508

American (AMR) AF: 0.136 AC: 2075 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.114 AC: 548 AN: 4824

European-Finnish (FIN) AF: 0.189 AC: 1989 AN: 10546

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9185 AN: 68002

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0644 Hom.: 79

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.47
PhyloP100		0.70
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: rs12477602; hg19: chr2-203338245;