rs138578000

Variant names:

• chr6-32974446-G-GT
• rs138578000
• NM_005104.4:c.30-14dupT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_005104.4(BRD2):​c.30-14dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,600,636 control chromosomes in the GnomAD database, including 853 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.031 (791 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.609
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 6-32974446-G-GT is Benign according to our data. Variant chr6-32974446-G-GT is described in ClinVar as [Benign]. Clinvar id is 1175005.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0236 (3599/152286) while in subpopulation SAS AF = 0.039 (188/4824). AF 95% confidence interval is 0.0344. There are 62 homozygotes in GnomAd4. There are 1719 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 62 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.30-14dupT		intron_variant	Intron 2 of 12	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.30-16_30-15insT		intron_variant	Intron 2 of 12	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3599 AN: 152168 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0244

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: 0.0268

GnomAD2 exomes AF: 0.0291 AC: 7115 AN: 244708 AF XY: 0.0302

Gnomad AFR exome AF: 0.00630

Gnomad AMR exome AF: 0.0251

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0135

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0350

GnomAD4 exome AF: 0.0314 AC: 45496 AN: 1448350 Hom.: 791 Cov.: 30 AF XY: 0.0320 AC XY: 22985 AN XY: 718630

African (AFR) AF: 0.00484 AC: 160 AN: 33054

American (AMR) AF: 0.0255 AC: 1117 AN: 43744

Ashkenazi Jewish (ASJ) AF: 0.0131 AC: 332 AN: 25424

East Asian (EAS) AF: 0.0162 AC: 637 AN: 39404

South Asian (SAS) AF: 0.0446 AC: 3809 AN: 85484

European-Finnish (FIN) AF: 0.0151 AC: 804 AN: 53150

Middle Eastern (MID) AF: 0.0106 AC: 59 AN: 5562

European-Non Finnish (NFE) AF: 0.0334 AC: 36888 AN: 1102822

Other (OTH) AF: 0.0283 AC: 1690 AN: 59706

GnomAD4 genome AF: 0.0236 AC: 3599 AN: 152286 Hom.: 62 Cov.: 32 AF XY: 0.0231 AC XY: 1719 AN XY: 74462

African (AFR) AF: 0.00647 AC: 269 AN: 41562

American (AMR) AF: 0.0243 AC: 372 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5178

South Asian (SAS) AF: 0.0390 AC: 188 AN: 4824

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2388 AN: 68010

Other (OTH) AF: 0.0265 AC: 56 AN: 2112

Alfa AF: 0.0291 Hom.: 16

Bravo AF: 0.0233

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs138578000; hg19: chr6-32942223;