Variant chr20-6779333-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001200.4(BMP2):c.*244A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 163,158 control chromosomes in the GnomAD database, including 4,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4607 hom., cov: 32)

Exomes 𝑓: 0.26 ( 386 hom. )

Consequence

BMP2
NM_001200.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.35

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 (BayesDel_noAF=-0.55).

BP6

Variant 20-6779333-A-C is Benign according to our data. Variant chr20-6779333-A-C is described in ClinVar as [Benign]. Clinvar id is 1169224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 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.*244A>C		3_prime_UTR_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.*244A>C		3_prime_UTR_variant	3/3	1	NM_001200.4	ENSP00000368104	P1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35844

AN:

151806

Hom.:

4602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.259

AC:

2906

AN:

11234

Hom.:

386

Cov.:

AF XY:

0.257

AC XY:

1622

AN XY:

6308

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.236

AC:

35877

AN:

151924

Hom.:

4607

Cov.:

AF XY:

0.239

AC XY:

17726

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.197

Hom.:

1189

Bravo

AF:

0.235

Asia WGS

AF:

0.402

AC:

1386

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	This variant is associated with the following publications: (PMID: 19492344, 20432245, 16497730, 27362534) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.90

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