chr20-6770235-T-G

Position:

chr20-6770235-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378827.5(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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 45 hom., cov: 32)

Exomes 𝑓: 0.021 ( 507 hom. )

Consequence

BMP2
ENST00000378827.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0510

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 195137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-6770235-T-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
BMP2	NM_001200.4 linkuse as main transcript	c.109T>G	p.Ser37Ala	missense_variant	2/3	ENST00000378827.5	NP_001191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP2	ENST00000378827.5 linkuse as main transcript	c.109T>G	p.Ser37Ala	missense_variant	2/3	1	NM_001200.4	ENSP00000368104	P1

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

GnomAD3 exomes

AF:

0.0236

AC:

5335

AN:

226254

Hom.:

131

AF XY:

0.0247

AC XY:

3055

AN XY:

123662

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 SAS exome

AF:

0.0442

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

Gnomad4 AFR exome

AF:

0.00226

Gnomad4 AMR exome

AF:

0.00765

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.0953

Gnomad4 SAS exome

AF:

0.0429

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0162

AC:

2470

AN:

152206

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1247

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.0843

Gnomad4 SAS

AF:

0.0499

Gnomad4 FIN

AF:

0.00942

Gnomad4 NFE

AF:

0.0185

Gnomad4 OTH

AF:

0.0195

Alfa

AF:

0.0198

Hom.:

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 08, 2014	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 14691541, 23506588) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ventricular septal defect 1

Benign:1

Benign, no assertion criteria provided

case-control

Cytogenetics- Mohapatra Lab, Banaras Hindu University

- -

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

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

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.16

REVEL

Benign

0.086

Sift

Benign

0.91

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.033

MPC

0.35

ClinPred

0.0023

GERP RS

-10

Varity_R

0.030

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over