Genetic Variant BMPR2:c.-933_-928dupGGCGGC (chr2-202376511-A-AGGCGGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001204.7(BMPR2):c.-933_-928dupGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 28 hom., cov: 16)

Consequence

BMPR2
NM_001204.7 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.67

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 -10 ACMG points.

BP6

Variant 2-202376511-A-AGGCGGC is Benign according to our data. Variant chr2-202376511-A-AGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1707255.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0161 (2028/125840) while in subpopulation AFR AF = 0.0207 (705/34004). AF 95% confidence interval is 0.0195. There are 28 homozygotes in GnomAd4. There are 949 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.

BS2

High AC in GnomAd4 at 2028 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.-933_-928dupGGCGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.-933_-928dupGGCGGC		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.-933_-928dupGGCGGC	5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4	Q13873-1
ENSG00000273456	ENST00000724884.1 link	n.154+274_154+279dupGCCGCC	intron_variant	Intron 1 of 1
ENSG00000273456	ENST00000724885.1 link	n.106+116_106+121dupGCCGCC	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2022

AN:

125736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00138

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00942

Gnomad EAS

AF:

0.00334

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0147

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.00835

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

GnomAD4 genome

AF:

0.0161

AC:

2028

AN:

125840

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

949

AN XY:

60228

show subpopulations

African (AFR)

AF:

0.0207

AC:

705

AN:

34004

American (AMR)

AF:

0.0126

AC:

149

AN:

11822

Ashkenazi Jewish (ASJ)

AF:

0.00942

AC:

AN:

3186

East Asian (EAS)

AF:

0.00335

AC:

AN:

4174

South Asian (SAS)

AF:

0.0112

AC:

AN:

2942

European-Finnish (FIN)

AF:

0.0221

AC:

182

AN:

8236

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0152

AC:

897

AN:

58916

Other (OTH)

AF:

0.00826

AC:

AN:

1574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00491

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 28, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

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

Publications

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chr2-202376511-A-AGGCGGC

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