6-32975374-T-C

Variant names:

• chr6-32975374-T-C
• rs635688
• NM_005104.4:c.334-10T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005104.4(BRD2):​c.334-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,594,642 control chromosomes in the GnomAD database, including 281,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.64 (31356 hom., cov: 29)
  • Exomes 𝑓: 0.59 (250639 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Scores: Splicing: ADA: 0.00009325
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.63
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-32975374-T-C is Benign according to our data. Variant chr6-32975374-T-C is described in ClinVar as [Benign]. Clinvar id is 3060819.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.334-10T>C		intron_variant	Intron 3 of 12	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.334-10T>C		intron_variant	Intron 3 of 12	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96314 AN: 151520 Hom.: 31314 Cov.: 29

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.631

GnomAD2 exomes AF: 0.582 AC: 138814 AN: 238484 AF XY: 0.578

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.510

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.517

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.587 AC: 847413 AN: 1443004 Hom.: 250639 Cov.: 33 AF XY: 0.586 AC XY: 420897 AN XY: 718382

African (AFR) AF: 0.785 AC: 25833 AN: 32888

American (AMR) AF: 0.510 AC: 22290 AN: 43686

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 15609 AN: 25940

East Asian (EAS) AF: 0.528 AC: 20906 AN: 39582

South Asian (SAS) AF: 0.529 AC: 44777 AN: 84664

European-Finnish (FIN) AF: 0.631 AC: 32834 AN: 52004

Middle Eastern (MID) AF: 0.590 AC: 3235 AN: 5480

European-Non Finnish (NFE) AF: 0.589 AC: 647133 AN: 1099034

Other (OTH) AF: 0.583 AC: 34796 AN: 59726

GnomAD4 genome AF: 0.636 AC: 96404 AN: 151638 Hom.: 31356 Cov.: 29 AF XY: 0.632 AC XY: 46789 AN XY: 74050

African (AFR) AF: 0.778 AC: 32112 AN: 41292

American (AMR) AF: 0.544 AC: 8289 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2580 AN: 5154

South Asian (SAS) AF: 0.523 AC: 2502 AN: 4786

European-Finnish (FIN) AF: 0.629 AC: 6584 AN: 10466

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40227 AN: 67912

Other (OTH) AF: 0.627 AC: 1321 AN: 2106

Alfa AF: 0.623 Hom.: 57382

Bravo AF: 0.636

Asia WGS AF: 0.551 AC: 1920 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BRD2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0050
DANN	Benign	0.42
PhyloP100		-5.6
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000093
dbscSNV1_RF	Benign	0.018
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: rs635688; hg19: chr6-32943151; COSMIC: COSV66372649; COSMIC: COSV66372649;