Variant chr6-32974525-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_005104.4(BRD2):c.93G>A(p.Lys31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,613,806 control chromosomes in the GnomAD database, including 285,876 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 ( 31482 hom., cov: 32)

Exomes 𝑓: 0.59 ( 254394 hom. )

Consequence

BRD2
NM_005104.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.534

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 6-32974525-G-A is Benign according to our data. Variant chr6-32974525-G-A is described in ClinVar as [Benign]. Clinvar id is 3058972.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-32974525-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.534 with no splicing effect.

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	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.93G>A	p.Lys31=	synonymous_variant	3/13	ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9 linkuse as main transcript	c.93G>A	p.Lys31=	synonymous_variant	3/13	1	NM_005104.4	P2	P25440-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96642

AN:

151978

Hom.:

31440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.632

GnomAD3 exomes

AF:

0.581

AC:

145931

AN:

251012

Hom.:

42989

AF XY:

0.577

AC XY:

78297

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.779

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.630

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.588

AC:

859631

AN:

1461710

Hom.:

254394

Cov.:

AF XY:

0.587

AC XY:

426461

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.786

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:

0.590

Gnomad4 OTH exome

AF:

0.584

GnomAD4 genome

AF:

0.636

AC:

96732

AN:

152096

Hom.:

31482

Cov.:

AF XY:

0.632

AC XY:

47010

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.543

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.502

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.596

Hom.:

44632

Bravo

AF:

0.636

Asia WGS

AF:

0.552

AC:

1924

AN:

3478

EpiCase

AF:

0.585

EpiControl

AF:

0.577

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BRD2-related disorder

Benign:1

Benign, criteria provided, single submitter

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

-0.57

CADD

Benign

6.7

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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