rs17840186

Positions:

• chr6-32970422-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005104.4(BRD2):​c.-1304-1173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,548 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (338 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4	c.-1304-1173G>A		intron_variant		ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.-1304-1173G>A		intron_variant		1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9775 AN: 152160 Hom.: 338 Cov.: 33

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0481 AC: 13 AN: 270 Hom.: 1 Cov.: 0 AF XY: 0.0561 AC XY: 12 AN XY: 214

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0446

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0642 AC: 9777 AN: 152278 Hom.: 338 Cov.: 33 AF XY: 0.0635 AC XY: 4726 AN XY: 74460

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0632

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0627 Hom.: 110

Bravo AF: 0.0651

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.97

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

Other links and lift over

dbSNP: rs17840186; hg19: chr6-32938199;