rs620202

Positions:

• chr6-32974133-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005104.4(BRD2):​c.30-329G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,068 control chromosomes in the GnomAD database, including 4,940 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 0.24 (4940 hom., cov: 32)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4	c.30-329G>T		intron_variant		ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.30-329G>T		intron_variant		1	NM_005104.4	ENSP00000363958	P2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35794 AN: 151950 Hom.: 4939 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35802 AN: 152068 Hom.: 4940 Cov.: 32 AF XY: 0.243 AC XY: 18069 AN XY: 74296

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.201

Alfa AF: 0.272 Hom.: 9874

Bravo AF: 0.208

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.76

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: rs620202; hg19: chr6-32941910;