rs3918142

chr6-32977921-TGAG-Tchr6-32977921-TGAG-TGAGGAG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_005104.4(BRD2):c.1500_1502del(p.Glu500del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0302 in 1,612,630 control chromosomes in the GnomAD database, including 928 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.022 (53 hom., cov: 32)
  • Exomes 𝑓: 0.031 (875 hom.)
• Consequence: BRD2 NM_005104.4 inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 5.63

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 -9 ACMG points.

• BP6: Variant 6-32977921-TGAG-T is Benign according to our data. Variant chr6-32977921-TGAG-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95243.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}. Variant chr6-32977921-TGAG-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0221 (3367/152014) while in subpopulation SAS AF= 0.0522 (251/4812). AF 95% confidence interval is 0.0469. There are 53 homozygotes in gnomad4. There are 1543 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD2	NM_005104.4	c.1500_1502del	p.Glu500del	inframe_deletion	9/13	ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9	c.1500_1502del	p.Glu500del	inframe_deletion	9/13	1	NM_005104.4	P2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3372 AN: 151894 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00590

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.00624

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.0256 AC: 6312 AN: 246560 Hom.: 137 AF XY: 0.0278 AC XY: 3740 AN XY: 134350

Gnomad AFR exome AF: 0.00549

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0461

Gnomad EAS exome AF: 0.0165

Gnomad SAS exome AF: 0.0481

Gnomad FIN exome AF: 0.00742

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0311 AC: 45361 AN: 1460616 Hom.: 875 AF XY: 0.0315 AC XY: 22917 AN XY: 726638

Gnomad4 AFR exome AF: 0.00612

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.0428

Gnomad4 EAS exome AF: 0.00778

Gnomad4 SAS exome AF: 0.0479

Gnomad4 FIN exome AF: 0.00806

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0301

GnomAD4 genome AF: 0.0221 AC: 3367 AN: 152014 Hom.: 53 Cov.: 32 AF XY: 0.0208 AC XY: 1543 AN XY: 74344

Gnomad4 AFR AF: 0.00591

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.00624

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0267 Hom.: 5

Bravo AF: 0.0215

EpiCase AF: 0.0328

EpiControl AF: 0.0343

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 03, 2013

- -

BRD2-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2019

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

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

Other links and lift over

dbSNP: rs3918142; hg19: chr6-32945698;