rs3918144

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005104.4(BRD2):c.146C>G(p.Ala49Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0155 in 1,614,232 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 32)

Exomes 𝑓: 0.016 ( 252 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046857).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0124 (1895/152348) while in subpopulation SAS AF = 0.029 (140/4824). AF 95% confidence interval is 0.0251. There are 18 homozygotes in GnomAd4. There are 951 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 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	UniProt
BRD2	NM_005104.4	MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 3 of 13	NP_005095.1	P25440-1
BRD2	NM_001199455.1		c.146C>G	p.Ala49Gly	missense	Exon 2 of 13	NP_001186384.1	P25440-2
BRD2	NM_001113182.3		c.146C>G	p.Ala49Gly	missense	Exon 3 of 13	NP_001106653.1	P25440-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRD2	ENST00000374825.9	TSL:1 MANE Select	c.146C>G	p.Ala49Gly	missense	Exon 3 of 13	ENSP00000363958.4	P25440-1
BRD2	ENST00000395287.5	TSL:1	c.146C>G	p.Ala49Gly	missense	Exon 2 of 13	ENSP00000378702.1	P25440-2
BRD2	ENST00000449025.5	TSL:1	c.161C>G	p.Ala54Gly	missense	Exon 2 of 12	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1897

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.0170

AC:

4282

AN:

251466

AF XY:

0.0188

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00969

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0159

AC:

23188

AN:

1461884

Hom.:

252

Cov.:

AF XY:

0.0165

AC XY:

12022

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00230

AC:

AN:

33480

American (AMR)

AF:

0.0103

AC:

461

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00968

AC:

253

AN:

26136

East Asian (EAS)

AF:

0.000907

AC:

AN:

39700

South Asian (SAS)

AF:

0.0359

AC:

3100

AN:

86258

European-Finnish (FIN)

AF:

0.0192

AC:

1023

AN:

53418

Middle Eastern (MID)

AF:

0.0238

AC:

137

AN:

5768

European-Non Finnish (NFE)

AF:

0.0154

AC:

17176

AN:

1112004

Other (OTH)

AF:

0.0153

AC:

925

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1447

2894

4342

5789

7236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.0124

AC:

1895

AN:

152348

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

951

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00286

AC:

119

AN:

41582

American (AMR)

AF:

0.0114

AC:

175

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00231

AC:

AN:

5194

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4824

European-Finnish (FIN)

AF:

0.0153

AC:

163

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0177

AC:

1201

AN:

68026

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

192

289

385

481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0163

Hom.:

Bravo

AF:

0.0117

ExAC

AF:

0.0180

AC:

2189

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0204

EpiControl

AF:

0.0194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PhyloP100

5.6

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.039

Sift4G

Benign

0.21

Polyphen

0.78

Vest4

0.50

ClinPred

0.019

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.35

Mutation Taster

=275/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over