6-32969311-CT-C

Position:

• chr6-32969311-CT-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000496118.2(BRD2):​c.67delT​(p.Tyr23fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000821 in 716,510 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: BRD2 ENST00000496118.2 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

Genes affected

BRD2 (HGNC:):

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-32969311-CT-C is Benign according to our data. Variant chr6-32969311-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3388364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4	c.-1305+256delT		intron_variant		ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.-1305+256delT		intron_variant		1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.00165 AC: 251 AN: 152024 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00891

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000787 AC: 115 AN: 146204 Hom.: 0 AF XY: 0.000824 AC XY: 65 AN XY: 78840

Gnomad AFR exome AF: 0.00297

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000186

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000130

Gnomad OTH exome AF: 0.000709

GnomAD4 exome AF: 0.000597 AC: 337 AN: 564368 Hom.: 2 Cov.: 0 AF XY: 0.000624 AC XY: 190 AN XY: 304572

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.00586

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000125

Gnomad4 SAS exome AF: 0.0000638

Gnomad4 FIN exome AF: 0.0000418

Gnomad4 NFE exome AF: 0.000174

Gnomad4 OTH exome AF: 0.000848

GnomAD4 genome AF: 0.00165 AC: 251 AN: 152142 Hom.: 2 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74390

Gnomad4 AFR AF: 0.00239

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.00199

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

BRD2: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs551724753; hg19: chr6-32937088;