Genetic Variant BRD2:c.-1304-1173G>A (chr6-32970422-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005104.4(BRD2):c.-1304-1173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,548 control chromosomes in the GnomAD database, including 339 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 0.064 ( 338 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1 hom. )

Consequence

BRD2
NM_005104.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.520

Publications

15 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:

ENSG00000223837 (HGNC:):

ENSG00000223837 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	NM_005104.4	MANE Select	c.-1304-1173G>A		intron	N/A	NP_005095.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BRD2	ENST00000374825.9	TSL:1 MANE Select	c.-1304-1173G>A	intron	N/A	ENSP00000363958.4
BRD2	ENST00000449085.4	TSL:1	c.-1305+1070G>A	intron	N/A	ENSP00000409145.3
BRD2	ENST00000678250.1		c.-1305+669G>A	intron	N/A	ENSP00000502900.1

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9775

AN:

152160

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0850

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0577

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.0446

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0632

GnomAD4 exome

AF:

0.0481

AC:

AN:

270

Hom.:

Cov.:

AF XY:

0.0561

AC XY:

AN XY:

214

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0446

AC:

AN:

202

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0642

AC:

9777

AN:

152278

Hom.:

338

Cov.:

AF XY:

0.0635

AC XY:

4726

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0849

AC:

3527

AN:

41546

American (AMR)

AF:

0.0576

AC:

882

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3470

East Asian (EAS)

AF:

0.0129

AC:

AN:

5186

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4830

European-Finnish (FIN)

AF:

0.0446

AC:

473

AN:

10610

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0632

AC:

4298

AN:

68016

Other (OTH)

AF:

0.0620

AC:

131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

465

929

1394

1858

2323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0618

Hom.:

679

Bravo

AF:

0.0651

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.52

PromoterAI

-0.075

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over