Variant 6-32974609-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005104.4(BRD2):c.177C>A(p.Ala59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,614,228 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 29 hom. )

Consequence

BRD2
NM_005104.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.331

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-32974609-C-A is Benign according to our data. Variant chr6-32974609-C-A is described in ClinVar as [Benign]. Clinvar id is 720050.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32974609-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.331 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4 linkuse as main transcript	c.177C>A	p.Ala59=	synonymous_variant	3/13	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.177C>A	p.Ala59=	synonymous_variant	3/13	1	NM_005104.4	ENSP00000363958	P2	P25440-1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00868

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00387

AC:

974

AN:

251488

Hom.:

AF XY:

0.00466

AC XY:

633

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00954

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00313

AC:

4573

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

2455

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00746

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00951

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00274

AC:

418

AN:

152336

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00869

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00307

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00545

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

-0.49

CADD

Benign

DANN

Benign

0.87

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