6-32974525-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31482 hom., cov: 32)
  • Exomes 𝑓: 0.59 (254394 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.534

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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	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	c.93G>A	p.Lys31=	synonymous_variant	3/13	1	NM_005104.4	P2

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96642 AN: 151978 Hom.: 31440 Cov.: 32

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

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.: 69 AF XY: 0.587 AC XY: 426461 AN XY: 727128

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.: 32 AF XY: 0.632 AC XY: 47010 AN XY: 74348

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

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

Other links and lift over

dbSNP: rs516535; hg19: chr6-32942302; COSMIC: COSV66372697; COSMIC: COSV66372697;