Genetic Variant BRD2:c.1330-4G>C (chr6-32977753-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005104.4(BRD2):c.1330-4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,612,886 control chromosomes in the GnomAD database, including 691,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.95 ( 68838 hom., cov: 32)

Exomes 𝑓: 0.92 ( 622981 hom. )

Consequence

BRD2
NM_005104.4 splice_region, intron

Scores

Splicing: ADA: 0.00001595

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.20

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 6-32977753-G-C is Benign according to our data. Variant chr6-32977753-G-C is described in ClinVar as [Benign]. Clinvar id is 95242.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4 link	c.1330-4G>C		splice_region_variant, intron_variant	Intron 8 of 12	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9 link	c.1330-4G>C		splice_region_variant, intron_variant	Intron 8 of 12	1	NM_005104.4	ENSP00000363958.4		P25440-1

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144575

AN:

152182

Hom.:

68775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.977

Gnomad ASJ

AF:

0.981

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.989

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.919

Gnomad OTH

AF:

0.962

GnomAD3 exomes

AF:

0.951

AC:

233590

AN:

245694

Hom.:

111220

AF XY:

0.951

AC XY:

127435

AN XY:

133950

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

0.994

Gnomad SAS exome

AF:

0.991

Gnomad FIN exome

AF:

0.926

Gnomad NFE exome

AF:

0.920

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.923

AC:

1348012

AN:

1460586

Hom.:

622981

Cov.:

AF XY:

0.925

AC XY:

672457

AN XY:

726600

show subpopulations

Gnomad4 AFR exome

AF:

0.987

Gnomad4 AMR exome

AF:

0.980

Gnomad4 ASJ exome

AF:

0.981

Gnomad4 EAS exome

AF:

0.995

Gnomad4 SAS exome

AF:

0.990

Gnomad4 FIN exome

AF:

0.924

Gnomad4 NFE exome

AF:

0.909

Gnomad4 OTH exome

AF:

0.932

GnomAD4 genome

AF:

0.950

AC:

144697

AN:

152300

Hom.:

68838

Cov.:

AF XY:

0.951

AC XY:

70858

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.984

Gnomad4 AMR

AF:

0.977

Gnomad4 ASJ

AF:

0.981

Gnomad4 EAS

AF:

0.993

Gnomad4 SAS

AF:

0.990

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.919

Gnomad4 OTH

AF:

0.963

Alfa

AF:

0.930

Hom.:

49163

Bravo

AF:

0.955

Asia WGS

AF:

0.985

AC:

3427

AN:

3478

EpiCase

AF:

0.927

EpiControl

AF:

0.930

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 03, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

BRD2-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.76

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over