rs2231342

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014482.3(BMP10):c.599C>G(p.Thr200Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00486 in 1,613,936 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 35 hom. )

Consequence

BMP10
NM_014482.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.09

Publications

11 publications found

Variant links:

Genes affected

BMP10 (HGNC:20869): (bone morphogenetic protein 10) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which binds to the activin receptor-like kinase 1 (ALK1) and plays important roles in cardiovascular development including cardiomyocyte proliferation and regulation of heart size, closure of the ductus arteriosus, angiogenesis and ventricular trabeculation. [provided by RefSeq, Aug 2016]

BMP10 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
left ventricular noncompaction
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
pulmonary arterial hypertension
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

BMP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.008932412).

BP6

Variant 2-68866307-G-C is Benign according to our data. Variant chr2-68866307-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 3236724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 581 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014482.3. 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
	BMP10	NM_014482.3	MANE Select	c.599C>G	p.Thr200Ser	missense	Exon 2 of 2	NP_055297.1	O95393

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP10	ENST00000295379.2	TSL:1 MANE Select	c.599C>G	p.Thr200Ser	missense	Exon 2 of 2	ENSP00000295379.1	O95393
	BMP10	ENST00000960265.1		c.335-15C>G		intron	N/A	ENSP00000630324.1

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00468

AC:

1176

AN:

251176

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00496

AC:

7255

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

3547

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33472

American (AMR)

AF:

0.00275

AC:

123

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00548

AC:

473

AN:

86258

European-Finnish (FIN)

AF:

0.00912

AC:

487

AN:

53420

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00528

AC:

5873

AN:

1111950

Other (OTH)

AF:

0.00437

AC:

264

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

476

951

1427

1902

2378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

220

440

660

880

1100

<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:

0.00382

AC:

581

AN:

152138

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

319

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000675

AC:

AN:

41488

American (AMR)

AF:

0.00334

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00353

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00521

AC:

354

AN:

68004

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00449

Hom.:

Bravo

AF:

0.00283

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00492

AC:

597

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00379

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bladder exstrophy-epispadias-cloacal extrophy complex (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.30

Eigen

Benign

-0.21

Eigen_PC

Benign

0.0099

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0089

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.81

PhyloP100

4.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.060

REVEL

Benign

0.10

Sift

Benign

0.37

Sift4G

Benign

0.52

Polyphen

0.0020

Vest4

0.038

MutPred

0.19

Loss of phosphorylation at T200 (P = 0.0754)

MVP

0.58

MPC

0.27

ClinPred

0.010

GERP RS

6.0

Varity_R

0.055

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over