rs1049007

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.261A>G(p.Ser87Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,632 control chromosomes in the GnomAD database, including 338,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38802 hom., cov: 32)

Exomes 𝑓: 0.64 ( 299243 hom. )

Consequence

BMP2
NM_001200.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.31

Publications

44 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: Labcorp Genetics (formerly Invitae), G2P
brachydactyly type A2
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

BMP2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001200.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.73).

BP6

Variant 20-6770387-A-G is Benign according to our data. Variant chr20-6770387-A-G is described in ClinVar as Benign. ClinVar VariationId is 195136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001200.4. 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
	BMP2	NM_001200.4	MANE Select	c.261A>G	p.Ser87Ser	synonymous	Exon 2 of 3	NP_001191.1	P12643

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMP2	ENST00000378827.5	TSL:1 MANE Select	c.261A>G	p.Ser87Ser	synonymous	Exon 2 of 3	ENSP00000368104.3	P12643
BMP2	ENST00000936876.1		c.261A>G	p.Ser87Ser	synonymous	Exon 1 of 2	ENSP00000606935.1
BMP2	ENST00000953442.1		c.261A>G	p.Ser87Ser	synonymous	Exon 2 of 3	ENSP00000623501.1

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107126

AN:

151936

Hom.:

38751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.858

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.720

GnomAD2 exomes

AF:

0.670

AC:

164002

AN:

244928

AF XY:

0.662

show subpopulations

Gnomad AFR exome

AF:

0.863

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.809

Gnomad EAS exome

AF:

0.830

Gnomad FIN exome

AF:

0.581

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.680

GnomAD4 exome

AF:

0.637

AC:

931010

AN:

1460578

Hom.:

299243

Cov.:

AF XY:

0.637

AC XY:

462704

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.869

AC:

29071

AN:

33464

American (AMR)

AF:

0.698

AC:

31208

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

21092

AN:

26120

East Asian (EAS)

AF:

0.823

AC:

32649

AN:

39684

South Asian (SAS)

AF:

0.610

AC:

52624

AN:

86244

European-Finnish (FIN)

AF:

0.587

AC:

30824

AN:

52494

Middle Eastern (MID)

AF:

0.765

AC:

4410

AN:

5766

European-Non Finnish (NFE)

AF:

0.620

AC:

688791

AN:

1111756

Other (OTH)

AF:

0.668

AC:

40341

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

21264

42528

63792

85056

106320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18610

37220

55830

74440

93050

<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:

0.705

AC:

107232

AN:

152054

Hom.:

38802

Cov.:

AF XY:

0.702

AC XY:

52154

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.858

AC:

35652

AN:

41532

American (AMR)

AF:

0.706

AC:

10792

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.817

AC:

2837

AN:

3472

East Asian (EAS)

AF:

0.820

AC:

4195

AN:

5114

South Asian (SAS)

AF:

0.611

AC:

2951

AN:

4828

European-Finnish (FIN)

AF:

0.581

AC:

6136

AN:

10562

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.623

AC:

42356

AN:

67940

Other (OTH)

AF:

0.722

AC:

1524

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1559

3117

4676

6234

7793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.655

Hom.:

55967

Bravo

AF:

0.724

Asia WGS

AF:

0.730

AC:

2535

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.647

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

(source)

DANN

Benign

0.49

PhyloP100

-1.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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