6-32968658-C-G

Position:

• chr6-32968658-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005104.4(BRD2):​c.-1703C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 153,654 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (63 hom., cov: 33)
  • Exomes 𝑓: 0.033 (0 hom.)
• Consequence: BRD2 NM_005104.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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]

HLA-DMA (HGNC:4934): (major histocompatibility complex, class II, DM alpha) HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0237 (3603/152316) while in subpopulation SAS AF= 0.039 (188/4824). AF 95% confidence interval is 0.0344. There are 63 homozygotes in gnomad4. There are 1726 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRD2	NM_005104.4	c.-1703C>G		5_prime_UTR_variant	1/13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825	c.-1703C>G		5_prime_UTR_variant	1/13	1	NM_005104.4	ENSP00000363958.4
HLA-DMA	ENST00000422832.1	c.-12+344G>C		intron_variant		6		ENSP00000403122.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3603 AN: 152198 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0329 AC: 44 AN: 1338 Hom.: 0 Cov.: 0 AF XY: 0.0359 AC XY: 37 AN XY: 1030

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0313

Gnomad4 SAS exome AF: 0.0327

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0337

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.0237 AC: 3603 AN: 152316 Hom.: 63 Cov.: 33 AF XY: 0.0232 AC XY: 1726 AN XY: 74474

Gnomad4 AFR AF: 0.00647

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0137 Hom.: 9

Bravo AF: 0.0233

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3918150; hg19: chr6-32936435;