Variant rs121908256 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PM5BP4_Strong

The ENST00000310942.9(CBX2):c.1328G>A(p.Arg443His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,609,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R443P) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CBX2
ENST00000310942.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.714

Variant links:

Genes affected

CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

CBX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-79784771-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 6827.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.027329206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CBX2	NM_005189.3 linkuse as main transcript	c.1328G>A	p.Arg443His	missense_variant	5/5	ENST00000310942.9	NP_005180.1
CBX2	XM_011525382.2 linkuse as main transcript	c.1328G>A	p.Arg443His	missense_variant	5/6		XP_011523684.1
CBX2	XM_011525383.3 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	5/6		XP_011523685.1
CBX2	XM_047436946.1 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	4/5		XP_047292902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX2	ENST00000310942.9 linkuse as main transcript	c.1328G>A	p.Arg443His	missense_variant	5/5	1	NM_005189.3	ENSP00000308750	P1	Q14781-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000208

AC:

AN:

239942

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

130720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1457748

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.52

DANN

Benign

0.39

DEOGEN2

Benign

0.048

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.66

M_CAP

Benign

0.0062

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.77

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

1.2

REVEL

Benign

0.074

Sift

Benign

1.0

Sift4G

Benign

0.59

Polyphen

0.0010

Vest4

0.039

MutPred

0.15

Loss of MoRF binding (P = 0.0373);

MVP

0.19

MPC

0.044

ClinPred

0.0086

GERP RS

-5.7

Varity_R

0.021

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over