NM_005104.4:c.610+34dupT

Variant names:

• chr6-32976202-C-CT
• rs2066741
• NM_005104.4:c.610+34dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005104.4(BRD2):​c.610+34dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,610,696 control chromosomes in the GnomAD database, including 195,390 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19347 hom., cov: 0)
  • Exomes 𝑓: 0.49 (176043 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 6 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

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.610+34dupT		intron	N/A	NP_005095.1	P25440-1
	BRD2	NM_001199455.1		c.610+34dupT		intron	N/A	NP_001186384.1	P25440-2
	BRD2	NM_001113182.3		c.610+34dupT		intron	N/A	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.610+34dupT		intron	N/A	ENSP00000363958.4	P25440-1
	BRD2	ENST00000395287.5	TSL:1	c.610+34dupT		intron	N/A	ENSP00000378702.1	P25440-2
	BRD2	ENST00000449025.5	TSL:1	c.625+34dupT		intron	N/A	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75910 AN: 151826 Hom.: 19335 Cov.: 0

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.470 AC: 115279 AN: 245122 AF XY: 0.468

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.488 AC: 711894 AN: 1458752 Hom.: 176043 Cov.: 45 AF XY: 0.486 AC XY: 352706 AN XY: 725474

African (AFR) AF: 0.544 AC: 18153 AN: 33362

American (AMR) AF: 0.374 AC: 16630 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13224 AN: 26038

East Asian (EAS) AF: 0.411 AC: 16290 AN: 39660

South Asian (SAS) AF: 0.393 AC: 33801 AN: 86090

European-Finnish (FIN) AF: 0.609 AC: 31848 AN: 52292

Middle Eastern (MID) AF: 0.476 AC: 2741 AN: 5762

European-Non Finnish (NFE) AF: 0.496 AC: 550701 AN: 1110760

Other (OTH) AF: 0.473 AC: 28506 AN: 60284

GnomAD4 genome AF: 0.500 AC: 75946 AN: 151944 Hom.: 19347 Cov.: 0 AF XY: 0.500 AC XY: 37093 AN XY: 74246

African (AFR) AF: 0.527 AC: 21820 AN: 41406

American (AMR) AF: 0.418 AC: 6386 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1802 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5172

South Asian (SAS) AF: 0.393 AC: 1894 AN: 4818

European-Finnish (FIN) AF: 0.611 AC: 6446 AN: 10542

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34145 AN: 67936

Other (OTH) AF: 0.484 AC: 1020 AN: 2108

Alfa AF: 0.513 Hom.: 3700

Bravo AF: 0.485

Asia WGS AF: 0.375 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs2066741; hg19: chr6-32943979; COSMIC: COSV104425873; COSMIC: COSV104425873;