3-23408436-C-G

Variant names:

• chr3-23408436-C-G
• rs2359763
• NM_152653.4:c.228-91172C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152653.4(UBE2E2):​c.228-91172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,024 control chromosomes in the GnomAD database, including 34,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34799 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.228-91172C>G		intron_variant	Intron 3 of 5	ENST00000396703.6	NP_689866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.228-91172C>G		intron_variant	Intron 3 of 5	1	NM_152653.4	ENSP00000379931.1
UBE2E2	ENST00000335798.8	n.228-124118C>G		intron_variant	Intron 3 of 4	1		ENSP00000338340.4
UBE2E2	ENST00000425792.5	c.228-91172C>G		intron_variant	Intron 3 of 5	2		ENSP00000401053.1
UBE2E2	ENST00000452894.5	c.299+84850C>G		intron_variant	Intron 4 of 5	3		ENSP00000392800.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100270 AN: 151906 Hom.: 34760 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.660 AC: 100359 AN: 152024 Hom.: 34799 Cov.: 32 AF XY: 0.657 AC XY: 48795 AN XY: 74278

African (AFR) AF: 0.885 AC: 36727 AN: 41500

American (AMR) AF: 0.481 AC: 7338 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3481 AN: 5184

South Asian (SAS) AF: 0.624 AC: 3008 AN: 4820

European-Finnish (FIN) AF: 0.641 AC: 6751 AN: 10526

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39088 AN: 67946

Other (OTH) AF: 0.634 AC: 1342 AN: 2116

Alfa AF: 0.467 Hom.: 1176

Bravo AF: 0.658

Asia WGS AF: 0.643 AC: 2234 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.57
DANN	Benign	0.51
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2359763; hg19: chr3-23449927;