chr2-202520065-T-TC

Variant names:

Variant summary

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

The NM_001204.7(BMPR2):c.853-21dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,484,684 control chromosomes in the GnomAD database, including 614 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 185 hom., cov: 22)

Exomes 𝑓: 0.036 ( 429 hom. )

Consequence

BMPR2
NM_001204.7 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.06

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-202520065-T-TC is Benign according to our data. Variant chr2-202520065-T-TC is described in ClinVar as Likely_benign. ClinVar VariationId is 257625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR2	NM_001204.7 link	c.853-21dupC		intron_variant	Intron 6 of 12	ENST00000374580.10	NP_001195.2	Q13873-1
BMPR2	XM_011511687.2 link	c.853-21dupC		intron_variant	Intron 6 of 12		XP_011509989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR2	ENST00000374580.10 link	c.853-22_853-21insC		intron_variant	Intron 6 of 12	1	NM_001204.7	ENSP00000363708.4		Q13873-1
BMPR2	ENST00000374574.2 link	c.853-22_853-21insC		intron_variant	Intron 6 of 11	2		ENSP00000363702.2		Q13873-2

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6430

AN:

151402

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.00813

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0466

GnomAD2 exomes

AF:

0.0356

AC:

8018

AN:

225004

AF XY:

0.0360

show subpopulations

Gnomad AFR exome

AF:

0.0469

Gnomad AMR exome

AF:

0.0318

Gnomad ASJ exome

AF:

0.0713

Gnomad EAS exome

AF:

0.000121

Gnomad FIN exome

AF:

0.00951

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0360

AC:

47976

AN:

1333168

Hom.:

429

Cov.:

AF XY:

0.0363

AC XY:

24328

AN XY:

669596

show subpopulations

African (AFR)

AF:

0.0483

AC:

1476

AN:

30564

American (AMR)

AF:

0.0312

AC:

1358

AN:

43466

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

1722

AN:

25214

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39078

South Asian (SAS)

AF:

0.0301

AC:

2478

AN:

82252

European-Finnish (FIN)

AF:

0.0105

AC:

530

AN:

50444

Middle Eastern (MID)

AF:

0.0803

AC:

441

AN:

5490

European-Non Finnish (NFE)

AF:

0.0377

AC:

37758

AN:

1000634

Other (OTH)

AF:

0.0395

AC:

2212

AN:

56026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

1637

3275

4912

6550

8187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1282

2564

3846

5128

6410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0424

AC:

6428

AN:

151516

Hom.:

185

Cov.:

AF XY:

0.0398

AC XY:

2951

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.0503

AC:

2080

AN:

41322

American (AMR)

AF:

0.0405

AC:

614

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

265

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.0337

AC:

161

AN:

4784

European-Finnish (FIN)

AF:

0.00813

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0424

AC:

2880

AN:

67856

Other (OTH)

AF:

0.0462

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

307

613

920

1226

1533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0225

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

May 24, 2021

GeneDx

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

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over