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rs13037675

chr20-6779059-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001200.4(BMP2):c.1161C>T(p.Asp387=) 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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.20
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-6779059-C-T is Benign according to our data. Variant chr20-6779059-C-T is described in ClinVar as [Benign]. Clinvar id is 257620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.2 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
BMP2NM_001200.4 linkuse as main transcriptc.1161C>T p.Asp387= synonymous_variant 3/3 ENST00000378827.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMP2ENST00000378827.5 linkuse as main transcriptc.1161C>T p.Asp387= synonymous_variant 3/31 NM_001200.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0636
AC:
9624
AN:
151264
Hom.:
369
Cov.:
31
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
GnomAD3 exomes
AF:
0.0695
AC:
17228
AN:
247714
Hom.:
916
AF XY:
0.0637
AC XY:
8543
AN XY:
134176
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 SAS exome
AF:
0.0230
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.:
35
AF XY:
0.0652
AC XY:
47295
AN XY:
725832
show subpopulations
Gnomad4 AFR exome
AF:
0.0467
Gnomad4 AMR exome
AF:
0.170
Gnomad4 ASJ exome
AF:
0.0334
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.0251
Gnomad4 FIN exome
AF:
0.0608
Gnomad4 NFE exome
AF:
0.0705
Gnomad4 OTH exome
AF:
0.0632
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0637
AC:
9640
AN:
151370
Hom.:
373
Cov.:
31
AF XY:
0.0632
AC XY:
4669
AN XY:
73918
show subpopulations
Gnomad4 AFR
AF:
0.0494
Gnomad4 AMR
AF:
0.124
Gnomad4 ASJ
AF:
0.0317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0256
Gnomad4 FIN
AF:
0.0546
Gnomad4 NFE
AF:
0.0700
Gnomad4 OTH
AF:
0.0669
Alfa
AF:
0.0596
Hom.:
146
Bravo
AF:
0.0699
Asia WGS
AF:
0.0160
AC:
56
AN:
3478
EpiCase
AF:
0.0651
EpiControl
AF:
0.0637

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJan 03, 2019- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
7.9
Dann
Benign
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13037675; hg19: chr20-6759706; API