Variant 6-32975374-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005104.4(BRD2):c.334-10T>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009325

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -5.63

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.334-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9 linkuse as main transcript	c.334-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005104.4	ENSP00000363958	P2	P25440-1

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

GnomAD3 exomes

AF:

0.582

AC:

138814

AN:

238484

Hom.:

40780

AF XY:

0.578

AC XY:

75166

AN XY:

130072

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 SAS exome

AF:

0.536

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

Gnomad4 AFR exome

AF:

0.785

Gnomad4 AMR exome

AF:

0.510

Gnomad4 ASJ exome

AF:

0.602

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.529

Gnomad4 FIN exome

AF:

0.631

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.583

GnomAD4 genome

AF:

0.636

AC:

96404

AN:

151638

Hom.:

31356

Cov.:

AF XY:

0.632

AC XY:

46789

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.627

Alfa

AF:

0.603

Hom.:

21918

Bravo

AF:

0.636

Asia WGS

AF:

0.551

AC:

1920

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BRD2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

-0.93

CADD

Benign

0.0050

DANN

Benign

0.42

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

1.8

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

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