20-6778468-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001200.4(BMP2):c.570A>T(p.Arg190Ser) variant causes a missense change. The variant allele was found at a frequency of 0.643 in 1,613,906 control chromosomes in the GnomAD database, including 339,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41279 hom., cov: 32)

Exomes 𝑓: 0.63 ( 297985 hom. )

Consequence

BMP2
NM_001200.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.90

Publications

111 publications found

Variant links:

Genes affected

BMP2 (HGNC:1069): (bone morphogenetic protein 2) 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 each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Duplication of a regulatory region downstream of this gene causes a form of brachydactyly characterized by a malformed index finger and second toe in human patients. [provided by RefSeq, Jul 2016]

BMP2 Gene-Disease associations (from GenCC):

short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
brachydactyly type A2
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

BMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.7473716E-6).

BP6

Variant 20-6778468-A-T is Benign according to our data. Variant chr20-6778468-A-T is described in ClinVar as Benign. ClinVar VariationId is 196322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4 link	c.570A>T	p.Arg190Ser	missense_variant	Exon 3 of 3	ENST00000378827.5	NP_001191.1	P12643C8C060

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5 link	c.570A>T	p.Arg190Ser	missense_variant	Exon 3 of 3	1	NM_001200.4	ENSP00000368104.3		P12643

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109818

AN:

151950

Hom.:

41224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.734

GnomAD2 exomes

AF:

0.671

AC:

168344

AN:

250820

AF XY:

0.662

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.812

Gnomad EAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.635

AC:

928160

AN:

1461838

Hom.:

297985

Cov.:

AF XY:

0.634

AC XY:

461020

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.941

AC:

31488

AN:

33478

American (AMR)

AF:

0.700

AC:

31318

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.810

AC:

21180

AN:

26136

East Asian (EAS)

AF:

0.813

AC:

32292

AN:

39700

South Asian (SAS)

AF:

0.609

AC:

52513

AN:

86258

European-Finnish (FIN)

AF:

0.581

AC:

31056

AN:

53418

Middle Eastern (MID)

AF:

0.765

AC:

4410

AN:

5768

European-Non Finnish (NFE)

AF:

0.615

AC:

683444

AN:

1111962

Other (OTH)

AF:

0.670

AC:

40459

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

22072

44143

66215

88286

110358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18530

37060

55590

74120

92650

<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:

0.723

AC:

109929

AN:

152068

Hom.:

41279

Cov.:

AF XY:

0.719

AC XY:

53404

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.928

AC:

38519

AN:

41516

American (AMR)

AF:

0.716

AC:

10944

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

2846

AN:

3470

East Asian (EAS)

AF:

0.813

AC:

4178

AN:

5142

South Asian (SAS)

AF:

0.612

AC:

2945

AN:

4812

European-Finnish (FIN)

AF:

0.571

AC:

6045

AN:

10578

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.620

AC:

42101

AN:

67956

Other (OTH)

AF:

0.736

AC:

1555

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1429

2858

4287

5716

7145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.659

Hom.:

10683

Bravo

AF:

0.744

TwinsUK

AF:

0.629

AC:

2331

ALSPAC

AF:

0.626

AC:

2412

ESP6500AA

AF:

0.928

AC:

4086

ESP6500EA

AF:

0.628

AC:

5398

ExAC

AF:

0.675

AC:

81894

Asia WGS

AF:

0.733

AC:

2546

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31640930, 26460254, 23506588) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 21, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0000027

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

PhyloP100

4.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.41

Sift

Benign

0.096

Sift4G

Uncertain

0.019

Polyphen

0.98

Vest4

0.32

MutPred

0.29

Gain of ubiquitination at K185 (P = 0.0445);

MPC

1.3

ClinPred

0.043

GERP RS

5.7

Varity_R

0.76

gMVP

0.70

Mutation Taster

=67/33

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over