rs10510536

Positions:

• chr3-23228279-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152653.4(UBE2E2):​c.227+10967T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,102 control chromosomes in the GnomAD database, including 2,344 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 0.16 (2344 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2E2	NM_152653.4	c.227+10967T>C		intron_variant		ENST00000396703.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2E2	ENST00000396703.6	c.227+10967T>C		intron_variant		1	NM_152653.4	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24775 AN: 151984 Hom.: 2342 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.163 AC: 24795 AN: 152102 Hom.: 2344 Cov.: 32 AF XY: 0.166 AC XY: 12380 AN XY: 74364

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.148

Alfa AF: 0.130 Hom.: 350

Bravo AF: 0.160

Asia WGS AF: 0.244 AC: 843 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs10510536; hg19: chr3-23269770;