NM_005104.4:c.93G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005104.4(BRD2):​c.93G>C​(p.Lys31Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K31K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRD2 NM_005104.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005104.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	NM_005104.4	MANE Select	c.93G>C	p.Lys31Asn	missense	Exon 3 of 13	NP_005095.1
	BRD2	NM_001199455.1		c.93G>C	p.Lys31Asn	missense	Exon 2 of 13	NP_001186384.1
	BRD2	NM_001113182.3		c.93G>C	p.Lys31Asn	missense	Exon 3 of 13	NP_001106653.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.93G>C	p.Lys31Asn	missense	Exon 3 of 13	ENSP00000363958.4
	BRD2	ENST00000395287.5	TSL:1	c.93G>C	p.Lys31Asn	missense	Exon 2 of 13	ENSP00000378702.1
	BRD2	ENST00000449025.5	TSL:1	c.108G>C	p.Lys36Asn	missense	Exon 2 of 12	ENSP00000409613.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.53
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Uncertain	0.010	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.28		Loss of ubiquitination at K31 (P = 0.0183)
MVP		0.71
ClinPred		0.93	D
GERP RS		2.9
Varity_R		0.092
gMVP		0.62
Mutation Taster		=82/18	polymorphism

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;