dbSNP rs635688: BRD2:c.334-10T>C (chr6-32975374-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005104.4(BRD2):c.334-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,594,642 control chromosomes in the GnomAD database, including 281,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.64 ( 31356 hom., cov: 29)

Exomes 𝑓: 0.59 ( 250639 hom. )

Consequence

BRD2
NM_005104.4 intron

Scores

Splicing: ADA: 0.00009325

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -5.63

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-32975374-T-C is Benign according to our data. Variant chr6-32975374-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060819.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRD2	NM_005104.4	MANE Select	c.334-10T>C	intron	N/A	NP_005095.1	P25440-1
BRD2	NM_001199455.1		c.334-10T>C	intron	N/A	NP_001186384.1	P25440-2
BRD2	NM_001113182.3		c.334-10T>C	intron	N/A	NP_001106653.1	P25440-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRD2	ENST00000374825.9	TSL:1 MANE Select	c.334-10T>C	intron	N/A	ENSP00000363958.4	P25440-1
BRD2	ENST00000395287.5	TSL:1	c.334-10T>C	intron	N/A	ENSP00000378702.1	P25440-2
BRD2	ENST00000449025.5	TSL:1	c.349-10T>C	intron	N/A	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96314

AN:

151520

Hom.:

31314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.631

GnomAD2 exomes

AF:

0.582

AC:

138814

AN:

238484

AF XY:

0.578

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.517

Gnomad FIN exome

AF:

0.631

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

AF:

0.587

AC:

847413

AN:

1443004

Hom.:

250639

Cov.:

AF XY:

0.586

AC XY:

420897

AN XY:

718382

show subpopulations

African (AFR)

AF:

0.785

AC:

25833

AN:

32888

American (AMR)

AF:

0.510

AC:

22290

AN:

43686

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

15609

AN:

25940

East Asian (EAS)

AF:

0.528

AC:

20906

AN:

39582

South Asian (SAS)

AF:

0.529

AC:

44777

AN:

84664

European-Finnish (FIN)

AF:

0.631

AC:

32834

AN:

52004

Middle Eastern (MID)

AF:

0.590

AC:

3235

AN:

5480

European-Non Finnish (NFE)

AF:

0.589

AC:

647133

AN:

1099034

Other (OTH)

AF:

0.583

AC:

34796

AN:

59726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15414

30828

46243

61657

77071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17690

35380

53070

70760

88450

<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:

0.636

AC:

96404

AN:

151638

Hom.:

31356

Cov.:

AF XY:

0.632

AC XY:

46789

AN XY:

74050

show subpopulations

African (AFR)

AF:

0.778

AC:

32112

AN:

41292

American (AMR)

AF:

0.544

AC:

8289

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2133

AN:

3468

East Asian (EAS)

AF:

0.501

AC:

2580

AN:

5154

South Asian (SAS)

AF:

0.523

AC:

2502

AN:

4786

European-Finnish (FIN)

AF:

0.629

AC:

6584

AN:

10466

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40227

AN:

67912

Other (OTH)

AF:

0.627

AC:

1321

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1686

3371

5057

6742

8428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.623

Hom.:

57382

Bravo

AF:

0.636

Asia WGS

AF:

0.551

AC:

1920

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BRD2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0050

(source)

DANN

Benign

0.42

PhyloP100

-5.6

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000093

dbscSNV1_RF

Benign

0.018

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

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