Variant 17-79778393-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005189.3(CBX2):c.82G>C(p.Glu28Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000077 in 1,428,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

CBX2
NM_005189.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.48

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX2	NM_005189.3 linkuse as main transcript	c.82G>C	p.Glu28Gln	missense_variant	2/5	ENST00000310942.9	NP_005180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX2	ENST00000310942.9 linkuse as main transcript	c.82G>C	p.Glu28Gln	missense_variant	2/5	1	NM_005189.3	ENSP00000308750	P1	Q14781-1
CBX2	ENST00000269399.5 linkuse as main transcript	c.82G>C	p.Glu28Gln	missense_variant	2/4	1		ENSP00000269399		Q14781-2
CBX2	ENST00000571484.1 linkuse as main transcript	n.155G>C		non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000770

AC:

AN:

1428186

Hom.:

Cov.:

AF XY:

0.00000985

AC XY:

AN XY:

710662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000909

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000839

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2022

The c.82G>C (p.E28Q) alteration is located in exon 2 (coding exon 2) of the CBX2 gene. This alteration results from a G to C substitution at nucleotide position 82, causing the glutamic acid (E) at amino acid position 28 to be replaced by a glutamine (Q). 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

0.96

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

-0.029

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.55

Sift

Benign

0.041

D;T

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.61

Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);

MVP

0.85

MPC

2.2

ClinPred

0.94

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over