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GeneBe

rs206781

chr6-32978356-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005104.4(BRD2):c.1809T>C(p.Ser603=) 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 (★).

Frequency

Genomes: 𝑓 0.32 ( 8470 hom., cov: 32)
Exomes 𝑓: 0.35 ( 94051 hom. )

Consequence

BRD2
NM_005104.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-32978356-T-C is Benign according to our data. Variant chr6-32978356-T-C is described in ClinVar as [Benign]. Clinvar id is 3059565.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.426 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
BRD2NM_005104.4 linkuse as main transcriptc.1809T>C p.Ser603= synonymous_variant 10/13 ENST00000374825.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRD2ENST00000374825.9 linkuse as main transcriptc.1809T>C p.Ser603= synonymous_variant 10/131 NM_005104.4 P2P25440-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.319
AC:
48531
AN:
151942
Hom.:
8470
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.342
AC:
83919
AN:
245206
Hom.:
15363
AF XY:
0.345
AC XY:
46206
AN XY:
133844
show subpopulations
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 SAS exome
AF:
0.324
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
show subpopulations
Gnomad4 AFR exome
AF:
0.193
Gnomad4 AMR exome
AF:
0.280
Gnomad4 ASJ exome
AF:
0.338
Gnomad4 EAS exome
AF:
0.213
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.513
Gnomad4 NFE exome
AF:
0.363
Gnomad4 OTH exome
AF:
0.326
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.319
AC:
48541
AN:
152060
Hom.:
8470
Cov.:
32
AF XY:
0.324
AC XY:
24084
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.202
Gnomad4 AMR
AF:
0.283
Gnomad4 ASJ
AF:
0.333
Gnomad4 EAS
AF:
0.190
Gnomad4 SAS
AF:
0.314
Gnomad4 FIN
AF:
0.515
Gnomad4 NFE
AF:
0.379
Gnomad4 OTH
AF:
0.277
Alfa
AF:
0.356
Hom.:
18347
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

BRD2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs206781; hg19: chr6-32946133; COSMIC: COSV66373502; COSMIC: COSV66373502; API