rs10510537

chr3-23280429-C-Achr3-23280429-C-T

Variant summary

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

The NM_152653.4(UBE2E2):c.227+63117C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 152,278 control chromosomes in the GnomAD database, including 108 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 0.029 (108 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2E2	NM_152653.4	c.227+63117C>A		intron_variant		ENST00000396703.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2E2	ENST00000396703.6	c.227+63117C>A		intron_variant		1	NM_152653.4	P1
UBE2E2	ENST00000335798.8	c.227+63117C>A		intron_variant, NMD_transcript_variant		1
UBE2E2	ENST00000425792.5	c.227+63117C>A		intron_variant		2		P1
UBE2E2	ENST00000452894.5	c.228-43086C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4381 AN: 152160 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0287 AC: 4376 AN: 152278 Hom.: 108 Cov.: 32 AF XY: 0.0288 AC XY: 2146 AN XY: 74454

Gnomad4 AFR AF: 0.00655

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0178 Hom.: 9

Bravo AF: 0.0303

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.72

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: rs10510537; hg19: chr3-23321920;