6-32974633-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005104.4(BRD2):c.201C>T(p.Ser67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,210 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (7 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0110

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 6-32974633-C-T is Benign according to our data. Variant chr6-32974633-C-T is described in ClinVar as [Benign]. Clinvar id is 772878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.011 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0054 (822/152316) while in subpopulation AFR AF= 0.0173 (719/41560). AF 95% confidence interval is 0.0163. There are 4 homozygotes in gnomad4. There are 396 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD2	NM_005104.4	c.201C>T	p.Ser67=	synonymous_variant	3/13	ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9	c.201C>T	p.Ser67=	synonymous_variant	3/13	1	NM_005104.4	P2

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 821 AN: 152198 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00161 AC: 406 AN: 251486 Hom.: 0 AF XY: 0.00142 AC XY: 193 AN XY: 135922

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000846 AC: 1237 AN: 1461894 Hom.: 7 Cov.: 33 AF XY: 0.000780 AC XY: 567 AN XY: 727248

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000289

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00540 AC: 822 AN: 152316 Hom.: 4 Cov.: 32 AF XY: 0.00532 AC XY: 396 AN XY: 74494

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00341 Hom.: 3

Bravo AF: 0.00618

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BRD2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.4
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs115120098; hg19: chr6-32942410;