Genetic Variant BRD2:p.Arg547Lys (chr6-32978187-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199455.1(BRD2):c.1640G>A(p.Arg547Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

BRD2
NM_001199455.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053037316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199455.1. 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.1640G>A	p.Arg547Lys	missense	Exon 10 of 13	NP_005095.1
BRD2	NM_001199455.1		c.1640G>A	p.Arg547Lys	missense	Exon 9 of 13	NP_001186384.1
BRD2	NM_001113182.3		c.1640G>A	p.Arg547Lys	missense	Exon 10 of 13	NP_001106653.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRD2	ENST00000374825.9	TSL:1 MANE Select	c.1640G>A	p.Arg547Lys	missense	Exon 10 of 13	ENSP00000363958.4
BRD2	ENST00000395287.5	TSL:1	c.1640G>A	p.Arg547Lys	missense	Exon 9 of 13	ENSP00000378702.1
BRD2	ENST00000449025.5	TSL:1	c.1655G>A	p.Arg552Lys	missense	Exon 9 of 12	ENSP00000409613.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245974

AF XY:

0.00000744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460754

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726694

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112002

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000540

Hom.:

ExAC

AF:

0.00000852

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.073

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

M_CAP

Benign

0.0024

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.83

PhyloP100

3.7

PrimateAI

Uncertain

0.74

PROVEAN

Benign

1.9

REVEL

Benign

0.084

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MutPred

0.070

Gain of methylation at R547 (P = 0.009)

MVP

0.63

ClinPred

0.29

GERP RS

4.5

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.3

Varity_R

0.10

gMVP

0.15

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over