NM_005104.4:c.402T>C

Variant names:

• chr6-32975452-T-C
• rs76146382
• NM_005104.4:c.402T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4 BP6_Moderate BP7 BS1 BS2

The NM_005104.4(BRD2):​c.402T>C​(p.Tyr134Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,612,534 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (110 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.414
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.196).
• BP6: Variant 6-32975452-T-C is Benign according to our data. Variant chr6-32975452-T-C is described in ClinVar as Benign. ClinVar VariationId is 770361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.414 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00303 (461/152288) while in subpopulation EAS AF = 0.0358 (186/5190). AF 95% confidence interval is 0.0316. There are 9 homozygotes in GnomAd4. There are 262 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.402T>C	p.Tyr134Tyr	synonymous	Exon 4 of 13	NP_005095.1	P25440-1
	BRD2	NM_001199455.1		c.402T>C	p.Tyr134Tyr	synonymous	Exon 3 of 13	NP_001186384.1	P25440-2
	BRD2	NM_001113182.3		c.402T>C	p.Tyr134Tyr	synonymous	Exon 4 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.402T>C	p.Tyr134Tyr	synonymous	Exon 4 of 13	ENSP00000363958.4	P25440-1
	BRD2	ENST00000395287.5	TSL:1	c.402T>C	p.Tyr134Tyr	synonymous	Exon 3 of 13	ENSP00000378702.1	P25440-2
	BRD2	ENST00000449025.5	TSL:1	c.417T>C	p.Tyr139Tyr	synonymous	Exon 3 of 12	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 462 AN: 152170 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.0359

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00851 AC: 2097 AN: 246354 AF XY: 0.00976

Gnomad AFR exome AF: 0.000662

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.00211

Gnomad EAS exome AF: 0.0494

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00136

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00335 AC: 4896 AN: 1460246 Hom.: 110 Cov.: 34 AF XY: 0.00431 AC XY: 3130 AN XY: 726484

African (AFR) AF: 0.000867 AC: 29 AN: 33464

American (AMR) AF: 0.00161 AC: 72 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00276 AC: 72 AN: 26126

East Asian (EAS) AF: 0.0203 AC: 807 AN: 39686

South Asian (SAS) AF: 0.0310 AC: 2676 AN: 86242

European-Finnish (FIN) AF: 0.000191 AC: 10 AN: 52314

Middle Eastern (MID) AF: 0.0153 AC: 88 AN: 5762

European-Non Finnish (NFE) AF: 0.000775 AC: 861 AN: 1111586

Other (OTH) AF: 0.00466 AC: 281 AN: 60350

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152288 Hom.: 9 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74478

African (AFR) AF: 0.000457 AC: 19 AN: 41548

American (AMR) AF: 0.000654 AC: 10 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.0358 AC: 186 AN: 5190

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68018

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00299

Asia WGS AF: 0.0170 AC: 58 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00225

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs76146382; hg19: chr6-32943229; COSMIC: COSV66373970; COSMIC: COSV66373970;