chr6-32969311-CT-C

Variant names:

• chr6-32969311-CT-C
• rs551724753
• ENST00000449085.4:c.-1345delT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005104.4(BRD2):​c.-1305+256delT variant causes a intron 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.-1305+256delT		intron_variant	Intron 1 of 12	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.-1305+256delT		intron_variant	Intron 1 of 12	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

GnomAD2 exomes AF: 0.000787 AC: 115 AN: 146204 AF XY: 0.000824

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 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

African (AFR) AF: 0.00272 AC: 43 AN: 15798

American (AMR) AF: 0.00586 AC: 203 AN: 34638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19974

East Asian (EAS) AF: 0.000125 AC: 4 AN: 32100

South Asian (SAS) AF: 0.0000638 AC: 4 AN: 62686

European-Finnish (FIN) AF: 0.0000418 AC: 2 AN: 47860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4046

European-Non Finnish (NFE) AF: 0.000174 AC: 55 AN: 316610

Other (OTH) AF: 0.000848 AC: 26 AN: 30656

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

African (AFR) AF: 0.00239 AC: 99 AN: 41506

American (AMR) AF: 0.00889 AC: 136 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67948

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

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

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BRD2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0
Mutation Taster		=73/127	disease causing

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

Other links and lift over

dbSNP: rs551724753; hg19: chr6-32937088;