Variant 6-32975452-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005104.4(BRD2):c.402T>C(p.Tyr134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,612,534 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 110 hom. )

Consequence

BRD2
NM_005104.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.414

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-32975452-T-C is Benign according to our data. Variant chr6-32975452-T-C is described in ClinVar as [Benign]. Clinvar id is 770361.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.414 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00303 (461/152288) while in subpopulation EAS AF= 0.0358 (186/5190). AF 95% confidence interval is 0.0316. There are 9 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.402T>C	p.Tyr134=	synonymous_variant	4/13	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.402T>C	p.Tyr134=	synonymous_variant	4/13	1	NM_005104.4	ENSP00000363958	P2	P25440-1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00851

AC:

2097

AN:

246354

Hom.:

AF XY:

0.00976

AC XY:

1310

AN XY:

134252

show subpopulations

Gnomad AFR exome

AF:

0.000662

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.0494

Gnomad SAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00335

AC:

4896

AN:

1460246

Hom.:

110

Cov.:

AF XY:

0.00431

AC XY:

3130

AN XY:

726484

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.0310

Gnomad4 FIN exome

AF:

0.000191

Gnomad4 NFE exome

AF:

0.000775

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152288

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.0358

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00299

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.70

CADD

Benign

5.1

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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