rs3918142

Variant names:

• chr6-32977921-TGAG-T
• rs3918142
• NM_005104.4:c.1500_1502delGGA

Your query was ambiguous. Multiple possible variants found:

• chr6-32977921-TGAG-T
• chr6-32977921-TGAG-TGAGGAG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_005104.4(BRD2):​c.1500_1502delGGA​(p.Glu500del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0302 in 1,612,630 control chromosomes in the GnomAD database, including 928 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (53 hom., cov: 32)
  • Exomes 𝑓: 0.031 (875 hom.)
• Consequence: BRD2 NM_005104.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 B:1
• Conservation: PhyloP100: 5.63
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005104.4
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0221 (3367/152014) while in subpopulation SAS AF = 0.0522 (251/4812). AF 95% confidence interval is 0.0469. There are 53 homozygotes in GnomAd4. There are 1543 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005104.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	NM_005104.4	MANE Select	c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	Exon 9 of 13	NP_005095.1	P25440-1
	BRD2	NM_001199455.1		c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	Exon 8 of 13	NP_001186384.1	P25440-2
	BRD2	NM_001113182.3		c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	Exon 9 of 13	NP_001106653.1	P25440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	Exon 9 of 13	ENSP00000363958.4	P25440-1
	BRD2	ENST00000395287.5	TSL:1	c.1500_1502delGGA	p.Glu500del	disruptive_inframe_deletion	Exon 8 of 13	ENSP00000378702.1	P25440-2
	BRD2	ENST00000449025.5	TSL:1	c.1515_1517delGGA	p.Glu505del	disruptive_inframe_deletion	Exon 8 of 12	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3372 AN: 151894 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00590

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.00624

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.0256 AC: 6312 AN: 246560 AF XY: 0.0278

Gnomad AFR exome AF: 0.00549

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0461

Gnomad EAS exome AF: 0.0165

Gnomad FIN exome AF: 0.00742

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0311 AC: 45361 AN: 1460616 Hom.: 875 AF XY: 0.0315 AC XY: 22917 AN XY: 726638

African (AFR) AF: 0.00612 AC: 205 AN: 33470

American (AMR) AF: 0.0113 AC: 506 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 1119 AN: 26136

East Asian (EAS) AF: 0.00778 AC: 309 AN: 39700

South Asian (SAS) AF: 0.0479 AC: 4135 AN: 86250

European-Finnish (FIN) AF: 0.00806 AC: 422 AN: 52328

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5768

European-Non Finnish (NFE) AF: 0.0330 AC: 36729 AN: 1111870

Other (OTH) AF: 0.0301 AC: 1819 AN: 60376

GnomAD4 genome AF: 0.0221 AC: 3367 AN: 152014 Hom.: 53 Cov.: 32 AF XY: 0.0208 AC XY: 1543 AN XY: 74344

African (AFR) AF: 0.00591 AC: 245 AN: 41458

American (AMR) AF: 0.0121 AC: 185 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5176

South Asian (SAS) AF: 0.0522 AC: 251 AN: 4812

European-Finnish (FIN) AF: 0.00624 AC: 66 AN: 10584

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2215 AN: 67930

Other (OTH) AF: 0.0161 AC: 34 AN: 2108

Alfa AF: 0.0267 Hom.: 5

Bravo AF: 0.0215

EpiCase AF: 0.0328

EpiControl AF: 0.0343

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	1	BRD2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6
Mutation Taster		=77/23	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3918142;

hg19: chr6-32945698;