20-6778468-A-T

Position:

chr20-6778468-A-T

Variant summary

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

The ENST00000378827.5(BMP2):c.570A>T(p.Arg190Ser) variant causes a missense change. The variant allele was found at a frequency of 0.643 in 1,613,906 control chromosomes in the GnomAD database, including 339,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 41279 hom., cov: 32)

Exomes 𝑓: 0.63 ( 297985 hom. )

Consequence

BMP2
ENST00000378827.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.90

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.7473716E-6).

BP6

Variant 20-6778468-A-T is Benign according to our data. Variant chr20-6778468-A-T is described in ClinVar as [Benign]. Clinvar id is 196322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 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.570A>T	p.Arg190Ser	missense_variant	3/3	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.570A>T	p.Arg190Ser	missense_variant	3/3	1	NM_001200.4	ENSP00000368104	P1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109818

AN:

151950

Hom.:

41224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.716

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.734

GnomAD3 exomes

AF:

0.671

AC:

168344

AN:

250820

Hom.:

57711

AF XY:

0.662

AC XY:

89964

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.812

Gnomad EAS exome

AF:

0.819

Gnomad SAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.626

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.635

AC:

928160

AN:

1461838

Hom.:

297985

Cov.:

AF XY:

0.634

AC XY:

461020

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.941

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.810

Gnomad4 EAS exome

AF:

0.813

Gnomad4 SAS exome

AF:

0.609

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.615

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.723

AC:

109929

AN:

152068

Hom.:

41279

Cov.:

AF XY:

0.719

AC XY:

53404

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.716

Gnomad4 ASJ

AF:

0.820

Gnomad4 EAS

AF:

0.813

Gnomad4 SAS

AF:

0.612

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.736

Alfa

AF:

0.659

Hom.:

10683

Bravo

AF:

0.744

TwinsUK

AF:

0.629

AC:

2331

ALSPAC

AF:

0.626

AC:

2412

ESP6500AA

AF:

0.928

AC:

4086

ESP6500EA

AF:

0.628

AC:

5398

ExAC

AF:

0.675

AC:

81894

Asia WGS

AF:

0.733

AC:

2546

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	This variant is associated with the following publications: (PMID: 31640930, 26460254, 23506588) -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 21, 2015	- -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.86

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0000027

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

6.4e-7

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.41

Sift

Benign

0.096

Sift4G

Uncertain

0.019

Polyphen

0.98

Vest4

0.32

MutPred

0.29

Gain of ubiquitination at K185 (P = 0.0445);

MPC

1.3

ClinPred

0.043

GERP RS

5.7

Varity_R

0.76

gMVP

0.70

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