Variant 20-6770387-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001200.4(BMP2):c.261A>G(p.Ser87=) 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP2	NM_001200.4 linkuse as main transcript	c.261A>G	p.Ser87=	synonymous_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.261A>G	p.Ser87=	synonymous_variant	2/3	1	NM_001200.4	ENSP00000368104	P1

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

GnomAD3 exomes

AF:

0.670

AC:

164002

AN:

244928

Hom.:

55757

AF XY:

0.662

AC XY:

88396

AN XY:

133542

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 SAS exome

AF:

0.606

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

Gnomad4 AFR exome

AF:

0.869

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.808

Gnomad4 EAS exome

AF:

0.823

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.587

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.705

AC:

107232

AN:

152054

Hom.:

38802

Cov.:

AF XY:

0.702

AC XY:

52154

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.858

Gnomad4 AMR

AF:

0.706

Gnomad4 ASJ

AF:

0.817

Gnomad4 EAS

AF:

0.820

Gnomad4 SAS

AF:

0.611

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.623

Gnomad4 OTH

AF:

0.722

Alfa

AF:

0.651

Hom.:

40254

Bravo

AF:

0.724

Asia WGS

AF:

0.730

AC:

2535

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.647

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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)	Oct 20, 2014	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

DANN

Benign

0.49

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