rs176250

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005104.4(BRD2):c.712C>T(p.Leu238Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,613,072 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 50 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.32

Publications

10 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048858523).

BP6

Variant 6-32976351-C-T is Benign according to our data. Variant chr6-32976351-C-T is described in ClinVar as Benign. ClinVar VariationId is 785805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005104.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRD2	NM_005104.4	MANE Select	c.712C>T	p.Leu238Phe	missense	Exon 6 of 13	NP_005095.1
BRD2	NM_001199455.1		c.712C>T	p.Leu238Phe	missense	Exon 5 of 13	NP_001186384.1
BRD2	NM_001113182.3		c.712C>T	p.Leu238Phe	missense	Exon 6 of 13	NP_001106653.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRD2	ENST00000374825.9	TSL:1 MANE Select	c.712C>T	p.Leu238Phe	missense	Exon 6 of 13	ENSP00000363958.4
BRD2	ENST00000395287.5	TSL:1	c.712C>T	p.Leu238Phe	missense	Exon 5 of 13	ENSP00000378702.1
BRD2	ENST00000449025.5	TSL:1	c.727C>T	p.Leu243Phe	missense	Exon 5 of 12	ENSP00000409613.1

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

730

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00639

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00527

AC:

1301

AN:

246892

AF XY:

0.00517

show subpopulations

Gnomad AFR exome

AF:

0.000527

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.00615

Gnomad OTH exome

AF:

0.00708

GnomAD4 exome

AF:

0.00461

AC:

6730

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3401

AN XY:

726698

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33480

American (AMR)

AF:

0.00143

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

977

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00213

AC:

184

AN:

86256

European-Finnish (FIN)

AF:

0.00373

AC:

195

AN:

52308

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00442

AC:

4911

AN:

1112004

Other (OTH)

AF:

0.00576

AC:

348

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

451

902

1352

1803

2254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00479

AC:

729

AN:

152310

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

41546

American (AMR)

AF:

0.00150

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00639

AC:

435

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.00470

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000993

AC:

ESP6500EA

AF:

0.00683

AC:

ExAC

AF:

0.00519

AC:

614

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00747

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

BRD2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.65

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

2.3

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.97

REVEL

Benign

0.11

Sift

Benign

0.35

Sift4G

Benign

0.26

Polyphen

0.81

Vest4

0.40

MVP

0.31

ClinPred

0.027

GERP RS

5.3

PromoterAI

-0.0072

Neutral

(source)

Varity_R

0.16

gMVP

0.24

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over