Variant 6-32974500-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005104.4(BRD2):c.68G>A(p.Gly23Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00717 in 1,613,526 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 60 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.96

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006654054).

BP6

Variant 6-32974500-G-A is Benign according to our data. Variant chr6-32974500-G-A is described in ClinVar as [Benign]. Clinvar id is 711314.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32974500-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.68G>A	p.Gly23Asp	missense_variant	3/13	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.68G>A	p.Gly23Asp	missense_variant	3/13	1	NM_005104.4	ENSP00000363958.4		P25440-1

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

943

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00575

AC:

1439

AN:

250376

Hom.:

AF XY:

0.00543

AC XY:

736

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.00907

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00728

AC:

10631

AN:

1461224

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

5173

AN XY:

726782

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.00838

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00620

AC:

944

AN:

152302

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00849

Hom.:

Bravo

AF:

0.00475

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00581

AC:

705

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;.;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;.;D;.

MetaRNN

Benign

0.0067

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.090

N;N;.;N

PROVEAN

Benign

-0.36

N;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.041

D;D;.;D

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.42

B;B;.;.

Vest4

0.63

MVP

0.41

ClinPred

0.033

GERP RS

5.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.25

gMVP

0.48

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