rs12822

Variant names:

• chr6-32977925-G-A
• rs12822
• NM_005104.4:c.1498G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32977925-G-A
• chr6-32977925-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005104.4(BRD2):​c.1498G>A​(p.Glu500Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,605,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BRD2 NM_005104.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15806013).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	NM_005104.4	MANE Select	c.1498G>A	p.Glu500Lys	missense	Exon 9 of 13	NP_005095.1
	BRD2	NM_001199455.1		c.1498G>A	p.Glu500Lys	missense	Exon 8 of 13	NP_001186384.1
	BRD2	NM_001113182.3		c.1498G>A	p.Glu500Lys	missense	Exon 9 of 13	NP_001106653.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.1498G>A	p.Glu500Lys	missense	Exon 9 of 13	ENSP00000363958.4
	BRD2	ENST00000395287.5	TSL:1	c.1498G>A	p.Glu500Lys	missense	Exon 8 of 13	ENSP00000378702.1
	BRD2	ENST00000449025.5	TSL:1	c.1513G>A	p.Glu505Lys	missense	Exon 8 of 12	ENSP00000409613.1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145504 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000314

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460288 Hom.: 0 Cov.: 58 AF XY: 0.00000275 AC XY: 2 AN XY: 726460

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111762

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145504 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71286

African (AFR) AF: 0.00 AC: 0 AN: 40926

American (AMR) AF: 0.00 AC: 0 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3154

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000314 AC: 2 AN: 63672

Other (OTH) AF: 0.00 AC: 0 AN: 2022

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.097
Eigen_PC	Benign	0.0040
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.083
Sift	Benign	0.061	T
Sift4G	Benign	0.14	T
Polyphen		0.26	B
Vest4		0.34
MutPred		0.28		Gain of methylation at E500 (P = 0.0115)
MVP		0.38
ClinPred		0.75	D
GERP RS		4.8
Varity_R		0.11
gMVP		0.12
Mutation Taster		=81/19	polymorphism

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: rs12822; hg19: chr6-32945702;