rs206781

Variant names:

• chr6-32978356-T-C
• rs206781
• NM_005104.4:c.1809T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005104.4(BRD2):​c.1809T>C​(p.Ser603Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,612,632 control chromosomes in the GnomAD database, including 102,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (8470 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94051 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.426
• Publications: 24 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).
• BP6: Variant 6-32978356-T-C is Benign according to our data. Variant chr6-32978356-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059565.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.426 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.1809T>C	p.Ser603Ser	synonymous_variant	Exon 10 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.1809T>C	p.Ser603Ser	synonymous_variant	Exon 10 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48531 AN: 151942 Hom.: 8470 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.342 AC: 83919 AN: 245206 AF XY: 0.345

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.174

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.353 AC: 515638 AN: 1460572 Hom.: 94051 Cov.: 58 AF XY: 0.354 AC XY: 257267 AN XY: 726596

African (AFR) AF: 0.193 AC: 6443 AN: 33466

American (AMR) AF: 0.280 AC: 12510 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8841 AN: 26132

East Asian (EAS) AF: 0.213 AC: 8467 AN: 39700

South Asian (SAS) AF: 0.318 AC: 27431 AN: 86242

European-Finnish (FIN) AF: 0.513 AC: 26816 AN: 52244

Middle Eastern (MID) AF: 0.340 AC: 1952 AN: 5744

European-Non Finnish (NFE) AF: 0.363 AC: 403486 AN: 1111960

Other (OTH) AF: 0.326 AC: 19692 AN: 60378

GnomAD4 genome AF: 0.319 AC: 48541 AN: 152060 Hom.: 8470 Cov.: 32 AF XY: 0.324 AC XY: 24084 AN XY: 74334

African (AFR) AF: 0.202 AC: 8366 AN: 41486

American (AMR) AF: 0.283 AC: 4320 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3468

East Asian (EAS) AF: 0.190 AC: 982 AN: 5170

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5445 AN: 10580

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25729 AN: 67942

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.346 Hom.: 30537

Bravo AF: 0.293

Asia WGS AF: 0.240 AC: 839 AN: 3478

EpiCase AF: 0.369

EpiControl AF: 0.357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BRD2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		-0.43
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=99/1	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: rs206781; hg19: chr6-32946133; COSMIC: COSV66373502; COSMIC: COSV66373502;