rs13037675

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001200.4(BMP2):c.1161C>T(p.Asp387Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,610,308 control chromosomes in the GnomAD database, including 4,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 373 hom., cov: 31)

Exomes 𝑓: 0.067 ( 3818 hom. )

Consequence

BMP2
NM_001200.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.20

Publications

14 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 20-6779059-C-T is Benign according to our data. Variant chr20-6779059-C-T is described in ClinVar as Benign. ClinVar VariationId is 257620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2	NM_001200.4 link	c.1161C>T	p.Asp387Asp	synonymous_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.1161C>T	p.Asp387Asp	synonymous_variant	Exon 3 of 3	1	NM_001200.4	ENSP00000368104.3		P12643

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9624

AN:

151264

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0493

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0546

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0700

Gnomad OTH

AF:

0.0675

GnomAD2 exomes

AF:

0.0695

AC:

17228

AN:

247714

AF XY:

0.0637

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.000762

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0687

Gnomad OTH exome

AF:

0.0703

GnomAD4 exome

AF:

0.0670

AC:

97699

AN:

1458938

Hom.:

3818

Cov.:

AF XY:

0.0652

AC XY:

47295

AN XY:

725832

show subpopulations

African (AFR)

AF:

0.0467

AC:

1562

AN:

33454

American (AMR)

AF:

0.170

AC:

7589

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

873

AN:

26100

East Asian (EAS)

AF:

0.000302

AC:

AN:

39698

South Asian (SAS)

AF:

0.0251

AC:

2168

AN:

86206

European-Finnish (FIN)

AF:

0.0608

AC:

3150

AN:

51780

Middle Eastern (MID)

AF:

0.0385

AC:

222

AN:

5764

European-Non Finnish (NFE)

AF:

0.0705

AC:

78309

AN:

1110884

Other (OTH)

AF:

0.0632

AC:

3814

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4094

8188

12282

16376

20470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2904

5808

8712

11616

14520

<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:

0.0637

AC:

9640

AN:

151370

Hom.:

373

Cov.:

AF XY:

0.0632

AC XY:

4669

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.0494

AC:

2038

AN:

41284

American (AMR)

AF:

0.124

AC:

1887

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.0256

AC:

122

AN:

4774

European-Finnish (FIN)

AF:

0.0546

AC:

565

AN:

10350

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0700

AC:

4748

AN:

67850

Other (OTH)

AF:

0.0669

AC:

140

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

446

892

1339

1785

2231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0599

Hom.:

207

Bravo

AF:

0.0699

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0651

EpiControl

AF:

0.0637

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.9

(source)

DANN

Benign

0.64

PhyloP100

2.2

Mutation Taster

=99/1

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