Genetic Variant BMPR2:c.-936_-928delGGCGGCGGC (chr2-202376511-AGGCGGCGGC-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001204.7(BMPR2):c.-936_-928delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0083 ( 11 hom., cov: 16)

Consequence

BMPR2
NM_001204.7 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.43

Publications

3 publications found

Variant links:

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

BMPR2 links:

ENSG00000273456 (HGNC:):

ENSG00000273456 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 2-202376511-AGGCGGCGGC-A is Benign according to our data. Variant chr2-202376511-AGGCGGCGGC-A is described in ClinVar as [Benign]. Clinvar id is 3041823.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00834 (1049/125852) while in subpopulation AFR AF = 0.0148 (503/34012). AF 95% confidence interval is 0.0137. There are 11 homozygotes in GnomAd4. There are 514 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.

BS2

High AC in GnomAd4 at 1049 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.-936_-928delGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.-936_-928delGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 13		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BMPR2	ENST00000374580.10 link	c.-936_-928delGGCGGCGGC	5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4	Q13873-1
ENSG00000273456	ENST00000724884.1 link	n.154+271_154+279delGCCGCCGCC	intron_variant	Intron 1 of 1
ENSG00000273456	ENST00000724885.1 link	n.106+113_106+121delGCCGCCGCC	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1049

AN:

125748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00138

Gnomad AMR

AF:

0.00932

Gnomad ASJ

AF:

0.00659

Gnomad EAS

AF:

0.00334

Gnomad SAS

AF:

0.00407

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00735

Gnomad NFE

AF:

0.00482

Gnomad OTH

AF:

0.00643

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

GnomAD4 genome

AF:

0.00834

AC:

1049

AN:

125852

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

514

AN XY:

60230

show subpopulations

African (AFR)

AF:

0.0148

AC:

503

AN:

34012

American (AMR)

AF:

0.00922

AC:

109

AN:

11820

Ashkenazi Jewish (ASJ)

AF:

0.00659

AC:

AN:

3186

East Asian (EAS)

AF:

0.00335

AC:

AN:

4174

South Asian (SAS)

AF:

0.00408

AC:

AN:

2942

European-Finnish (FIN)

AF:

0.0112

AC:

AN:

8244

Middle Eastern (MID)

AF:

0.00769

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00482

AC:

284

AN:

58914

Other (OTH)

AF:

0.00699

AC:

AN:

1574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00175

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMPR2-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-202376511-AGGCGGCGGC-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over