Variant chr6-32976246-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005104.4(BRD2):c.611-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,605,152 control chromosomes in the GnomAD database, including 34 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 0.0025 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 30 hom. )

Consequence

BRD2
NM_005104.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001694

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.53

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-32976246-C-G is Benign according to our data. Variant chr6-32976246-C-G is described in ClinVar as [Benign]. Clinvar id is 770728.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32976246-C-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.611-4C>G		splice_region_variant, 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.611-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005104.4	ENSP00000363958	P2	P25440-1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

378

AN:

151828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00446

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00235

AC:

567

AN:

240906

Hom.:

AF XY:

0.00228

AC XY:

299

AN XY:

131412

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.000208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.00438

Gnomad OTH exome

AF:

0.00272

GnomAD4 exome

AF:

0.00453

AC:

6583

AN:

1453206

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

3170

AN XY:

722774

show subpopulations

Gnomad4 AFR exome

AF:

0.000947

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.000348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000574

Gnomad4 NFE exome

AF:

0.00551

Gnomad4 OTH exome

AF:

0.00577

GnomAD4 genome

AF:

0.00249

AC:

378

AN:

151946

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00446

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.00275

EpiCase

AF:

0.00327

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BRD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.21

DANN

Benign

0.66

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.010

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