Variant chr6-32977921-TGAG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_005104.4(BRD2):c.1500_1502delGGA(p.Glu500del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0302 in 1,612,630 control chromosomes in the GnomAD database, including 928 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.022 ( 53 hom., cov: 32)

Exomes 𝑓: 0.031 ( 875 hom. )

Consequence

BRD2
NM_005104.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2B:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

BRD2 (HGNC:1103): (bromodomain containing 2) This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

BRD2 links:

BRD2 (HGNC:):

BRD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0221 (3367/152014) while in subpopulation SAS AF= 0.0522 (251/4812). AF 95% confidence interval is 0.0469. There are 53 homozygotes in gnomad4. There are 1543 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 53 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	9/13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9 linkuse as main transcript	c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	9/13	1	NM_005104.4	ENSP00000363958.4		P25440-1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3372

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00590

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0256

AC:

6312

AN:

246560

Hom.:

137

AF XY:

0.0278

AC XY:

3740

AN XY:

134350

show subpopulations

Gnomad AFR exome

AF:

0.00549

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0461

Gnomad EAS exome

AF:

0.0165

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.00742

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0311

AC:

45361

AN:

1460616

Hom.:

875

AF XY:

0.0315

AC XY:

22917

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.00612

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0428

Gnomad4 EAS exome

AF:

0.00778

Gnomad4 SAS exome

AF:

0.0479

Gnomad4 FIN exome

AF:

0.00806

Gnomad4 NFE exome

AF:

0.0330

Gnomad4 OTH exome

AF:

0.0301

GnomAD4 genome

AF:

0.0221

AC:

3367

AN:

152014

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1543

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00591

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.0522

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0267

Hom.:

Bravo

AF:

0.0215

EpiCase

AF:

0.0328

EpiControl

AF:

0.0343

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2013	- -

BRD2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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