chr6-32974500-G-A

Variant names:

• chr6-32974500-G-A
• rs55650502
• NM_005104.4:c.68G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005104.4(BRD2):​c.68G>A​(p.Gly23Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00717 in 1,613,526 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (60 hom.)
• Consequence: BRD2 NM_005104.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.96
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006654054).
• BP6: Variant 6-32974500-G-A is Benign according to our data. Variant chr6-32974500-G-A is described in ClinVar as [Benign]. Clinvar id is 711314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.68G>A	p.Gly23Asp	missense_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.68G>A	p.Gly23Asp	missense_variant	Exon 3 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 943 AN: 152184 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00575 AC: 1439 AN: 250376 AF XY: 0.00543

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.00907

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.00728 AC: 10631 AN: 1461224 Hom.: 60 Cov.: 31 AF XY: 0.00712 AC XY: 5173 AN XY: 726782

African (AFR) AF: 0.00125 AC: 42 AN: 33474

American (AMR) AF: 0.000962 AC: 43 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.0149 AC: 794 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00838 AC: 9309 AN: 1111424

Other (OTH) AF: 0.00618 AC: 373 AN: 60382

GnomAD4 genome AF: 0.00620 AC: 944 AN: 152302 Hom.: 8 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74482

African (AFR) AF: 0.00103 AC: 43 AN: 41550

American (AMR) AF: 0.00261 AC: 40 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0103 AC: 704 AN: 68024

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00810 Hom.: 16

Bravo AF: 0.00475

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00744 AC: 64

ExAC AF: 0.00581 AC: 705

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00834

EpiControl AF: 0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	.;.;D;.
MetaRNN	Benign	0.0067	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.090	N;N;.;N
PhyloP100		5.0
PROVEAN	Benign	-0.36	N;N;.;N
REVEL	Benign	0.13
Sift	Benign	0.041	D;D;.;D
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.42	B;B;.;.
Vest4		0.63
MVP		0.41
ClinPred		0.033	T
GERP RS		5.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.25
gMVP		0.48
Mutation Taster		=299/1	polymorphism

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: rs55650502; hg19: chr6-32942277; COSMIC: COSV99058766; COSMIC: COSV99058766;