20-6770235-T-G

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.109T>G(p.Ser37Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,603,848 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 45 hom., cov: 32)

Exomes 𝑓: 0.021 ( 507 hom. )

Consequence

BMP2
NM_001200.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0510

Publications

49 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=0.001722455).

BP6

Variant 20-6770235-T-G is Benign according to our data. Variant chr20-6770235-T-G is described in ClinVar as Benign. ClinVar VariationId is 195137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4 link	c.109T>G	p.Ser37Ala	missense_variant	Exon 2 of 3	ENST00000378827.5	NP_001191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5 link	c.109T>G	p.Ser37Ala	missense_variant	Exon 2 of 3	1	NM_001200.4	ENSP00000368104.3

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2468

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.0178

GnomAD2 exomes

AF:

0.0236

AC:

5335

AN:

226254

AF XY:

0.0247

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.00710

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.0923

Gnomad FIN exome

AF:

0.00977

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0211

AC:

30610

AN:

1451642

Hom.:

507

Cov.:

AF XY:

0.0217

AC XY:

15629

AN XY:

721436

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

33176

American (AMR)

AF:

0.00765

AC:

335

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.0315

AC:

817

AN:

25920

East Asian (EAS)

AF:

0.0953

AC:

3697

AN:

38790

South Asian (SAS)

AF:

0.0429

AC:

3638

AN:

84850

European-Finnish (FIN)

AF:

0.0101

AC:

522

AN:

51676

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0182

AC:

20124

AN:

1107770

Other (OTH)

AF:

0.0220

AC:

1319

AN:

59890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1967

3934

5902

7869

9836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.0162

AC:

2470

AN:

152206

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1247

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00308

AC:

128

AN:

41560

American (AMR)

AF:

0.0101

AC:

155

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

109

AN:

3466

East Asian (EAS)

AF:

0.0843

AC:

434

AN:

5150

South Asian (SAS)

AF:

0.0499

AC:

241

AN:

4826

European-Finnish (FIN)

AF:

0.00942

AC:

100

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0185

AC:

1256

AN:

67980

Other (OTH)

AF:

0.0195

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

121

242

363

484

605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0201

Hom.:

124

Bravo

AF:

0.0150

TwinsUK

AF:

0.0202

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.00387

AC:

ESP6500EA

AF:

0.0164

AC:

141

ExAC

AF:

0.0214

AC:

2583

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Oct 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

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

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 14691541, 23506588)

Ventricular septal defect 1

Benign:1

Cytogenetics- Mohapatra Lab, Banaras Hindu University

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:case-control

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.8

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.39

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.11

PhyloP100

-0.051

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.16

REVEL

Benign

0.086

Sift

Benign

0.91

Sift4G

Benign

0.62

Vest4

0.033

ClinPred

0.0023

GERP RS

-10

Varity_R

0.030

gMVP

0.28

Mutation Taster

=92/8

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