rs778064596

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005104.4(BRD2):c.361A>G(p.Met121Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

BRD2
NM_005104.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Publications

1 publications found

Variant links:

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]

BRD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4 link	c.361A>G	p.Met121Val	missense_variant	Exon 4 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9 link	c.361A>G	p.Met121Val	missense_variant	Exon 4 of 13	1	NM_005104.4	ENSP00000363958.4		P25440-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000813

AC:

AN:

246018

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456888

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

1108654

Other (OTH)

AF:

0.00

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000170

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.361A>G (p.M121V) alteration is located in exon 3 (coding exon 3) of the BRD2 gene. This alteration results from a A to G substitution at nucleotide position 361, causing the methionine (M) at amino acid position 121 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;.;.;.

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

.;.;D;.;.

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.93

D;D;D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.8

M;M;.;M;.

PhyloP100

9.3

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.8

D;D;.;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0010

D;D;.;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.90

MutPred

0.84

Loss of disorder (P = 0.112);Loss of disorder (P = 0.112);Loss of disorder (P = 0.112);Loss of disorder (P = 0.112);.;

MVP

0.81

ClinPred

0.98

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.81

Mutation Taster

=21/179

disease causing

(source)

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

Publications

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rs778064596

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over