chr6-32974525-G-A

Variant names:

• chr6-32974525-G-A
• rs516535
• NM_005104.4:c.93G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_005104.4(BRD2):​c.93G>A​(p.Lys31Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,613,806 control chromosomes in the GnomAD database, including 285,876 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 (31482 hom., cov: 32)
  • Exomes 𝑓: 0.59 (254394 hom.)
• Consequence: BRD2 NM_005104.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.534
• Publications: 39 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.089).
• BP6: Variant 6-32974525-G-A is Benign according to our data. Variant chr6-32974525-G-A is described in ClinVar as [Benign]. Clinvar id is 3058972.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• 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.93G>A	p.Lys31Lys	synonymous_variant	Exon 3 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.93G>A	p.Lys31Lys	synonymous_variant	Exon 3 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96642 AN: 151978 Hom.: 31440 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.632

GnomAD2 exomes AF: 0.581 AC: 145931 AN: 251012 AF XY: 0.577

Gnomad AFR exome AF: 0.779

Gnomad AMR exome AF: 0.509

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.515

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.588 AC: 859631 AN: 1461710 Hom.: 254394 Cov.: 69 AF XY: 0.587 AC XY: 426461 AN XY: 727128

African (AFR) AF: 0.786 AC: 26298 AN: 33474

American (AMR) AF: 0.510 AC: 22822 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 15740 AN: 26136

East Asian (EAS) AF: 0.528 AC: 20964 AN: 39696

South Asian (SAS) AF: 0.529 AC: 45615 AN: 86256

European-Finnish (FIN) AF: 0.631 AC: 33714 AN: 53420

Middle Eastern (MID) AF: 0.588 AC: 3391 AN: 5766

European-Non Finnish (NFE) AF: 0.590 AC: 655848 AN: 1111852

Other (OTH) AF: 0.584 AC: 35239 AN: 60388

GnomAD4 genome AF: 0.636 AC: 96732 AN: 152096 Hom.: 31482 Cov.: 32 AF XY: 0.632 AC XY: 47010 AN XY: 74348

African (AFR) AF: 0.778 AC: 32295 AN: 41512

American (AMR) AF: 0.543 AC: 8306 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2591 AN: 5164

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4822

European-Finnish (FIN) AF: 0.630 AC: 6660 AN: 10574

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

European-Non Finnish (NFE) AF: 0.592 AC: 40248 AN: 67952

Other (OTH) AF: 0.629 AC: 1325 AN: 2108

Alfa AF: 0.607 Hom.: 103401

Bravo AF: 0.636

Asia WGS AF: 0.552 AC: 1924 AN: 3478

EpiCase AF: 0.585

EpiControl AF: 0.577

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	-0.57
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		0.53
Mutation Taster		=295/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs516535; hg19: chr6-32942302; COSMIC: COSV66372697; COSMIC: COSV66372697;