Variant 3-23499684-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152653.4(UBE2E2):c.304G>C(p.Gly102Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

UBE2E2
NM_152653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

Variant links:

Genes affected

UBE2E2 (HGNC:12478): (ubiquitin conjugating enzyme E2 E2) Enables ISG15 transferase activity and ubiquitin conjugating enzyme activity. Involved in protein modification by small protein conjugation. Acts upstream of or within cellular response to DNA damage stimulus and positive regulation of G1/S transition of mitotic cell cycle. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBE2E2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2E2	NM_152653.4 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6	ENST00000396703.6	NP_689866.1	Q96LR5
UBE2E2	NM_001370225.1 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6		NP_001357154.1
UBE2E2	NM_001370226.1 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6		NP_001357155.1
UBE2E2	XM_047448843.1 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6		XP_047304799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBE2E2	ENST00000396703.6 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6	1	NM_152653.4	ENSP00000379931.1	Q96LR5
UBE2E2	ENST00000335798.8 linkuse as main transcript	n.228-32870G>C		intron_variant		1		ENSP00000338340.4	F8W8F0
UBE2E2	ENST00000425792.5 linkuse as main transcript	c.304G>C	p.Gly102Arg	missense_variant	4/6	2		ENSP00000401053.1	Q96LR5
UBE2E2	ENST00000452894.5 linkuse as main transcript	c.376G>C	p.Gly126Arg	missense_variant	5/6	3		ENSP00000392800.1	C9J180

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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

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 25, 2023

The c.304G>C (p.G102R) alteration is located in exon 4 (coding exon 3) of the UBE2E2 gene. This alteration results from a G to C substitution at nucleotide position 304, causing the glycine (G) at amino acid position 102 to be replaced by an arginine (R). 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

1.0

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;.;T;.

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

.;D;D;D

M_CAP

Pathogenic

0.38

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Pathogenic

0.89

MutationAssessor

Pathogenic

4.0

H;.;H;.

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-7.8

D;D;D;.

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0040

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.98

MutPred

0.89

Loss of catalytic residue at V103 (P = 0.0326);.;Loss of catalytic residue at V103 (P = 0.0326);.;

MVP

0.94

MPC

2.5

ClinPred

1.0

GERP RS

5.7

Varity_R

0.94

gMVP

0.98

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over