Genetic Variant NM_001204.7:c.-930_-928dupGGC (chr2-202376511-A-AGGC) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001204.7(BMPR2):c.-930_-928dupGGC 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 0.072 ( 387 hom., cov: 16)

Consequence

BMPR2
NM_001204.7 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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 -16 ACMG points.

BP6

Variant 2-202376511-A-AGGC is Benign according to our data. Variant chr2-202376511-A-AGGC is described in ClinVar as [Likely_benign]. Clinvar id is 333617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.-930_-928dupGGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.-930_-928dupGGC		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.-930_-928dupGGC	5_prime_UTR_variant	Exon 1 of 13	1	NM_001204.7	ENSP00000363708.4	Q13873-1
ENSG00000273456	ENST00000724884.1 link	n.154+277_154+279dupGCC	intron_variant	Intron 1 of 1
ENSG00000273456	ENST00000724885.1 link	n.106+119_106+121dupGCC	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

9008

AN:

125692

Hom.:

388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0581

Gnomad ASJ

AF:

0.0895

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.0995

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.107

Gnomad NFE

AF:

0.0793

Gnomad OTH

AF:

0.0567

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

GnomAD4 genome

AF:

0.0717

AC:

9017

AN:

125796

Hom.:

387

Cov.:

AF XY:

0.0682

AC XY:

4106

AN XY:

60210

show subpopulations

African (AFR)

AF:

0.0653

AC:

2219

AN:

33986

American (AMR)

AF:

0.0577

AC:

682

AN:

11816

Ashkenazi Jewish (ASJ)

AF:

0.0895

AC:

285

AN:

3184

East Asian (EAS)

AF:

0.0843

AC:

352

AN:

4174

South Asian (SAS)

AF:

0.0986

AC:

290

AN:

2942

European-Finnish (FIN)

AF:

0.0466

AC:

384

AN:

8244

Middle Eastern (MID)

AF:

0.109

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0793

AC:

4669

AN:

58896

Other (OTH)

AF:

0.0561

AC:

AN:

1570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

379

758

1136

1515

1894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0199

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 20, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pulmonary hypertension, primary, 1

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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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NM_001204.7:c.-930_-928dupGGC

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