5-139569777-G-T

Variant names:

• chr5-139569777-G-T
• rs261532
• NM_003339.3:c.24+7962G>T

Variant summary

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

The NM_003339.3(UBE2D2):​c.24+7962G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,034 control chromosomes in the GnomAD database, including 20,305 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 0.45 (20305 hom., cov: 32)
• Consequence: UBE2D2 NM_003339.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 23 publications found

Genes affected

UBE2D2 (HGNC:12475): (ubiquitin conjugating enzyme E2 D2) Regulated degradation of misfolded, damaged or short-lived proteins in eukaryotes occurs via the ubiquitin (Ub)-proteasome system (UPS). An integral part of the UPS system is the ubiquitination of target proteins and covalent linkage of Ub-containing proteins to form polymeric chains, marking them as targets for 26S proteasome-mediated degradation. Ubiquitination of proteins is mediated by a cascade of enzymes which includes E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligases) enzymes. This gene encodes a member of the E2 enzyme family. Substrates of this enzyme include the tumor suppressor protein p53 and peroxisomal biogenesis factor 5 (PEX5). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2D2	NM_003339.3	c.24+7962G>T		intron_variant	Intron 1 of 6	ENST00000398733.8	NP_003330.1
UBE2D2	NM_181838.2	c.-64+7370G>T		intron_variant	Intron 2 of 7		NP_862821.1
UBE2D2	XM_047417691.1	c.-63-30595G>T		intron_variant	Intron 1 of 6		XP_047273647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2D2	ENST00000398733.8	c.24+7962G>T		intron_variant	Intron 1 of 6	1	NM_003339.3	ENSP00000381717.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68228 AN: 151916 Hom.: 20247 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.449 AC: 68339 AN: 152034 Hom.: 20305 Cov.: 32 AF XY: 0.440 AC XY: 32694 AN XY: 74314

African (AFR) AF: 0.851 AC: 35307 AN: 41498

American (AMR) AF: 0.321 AC: 4903 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1386 AN: 3464

East Asian (EAS) AF: 0.144 AC: 745 AN: 5176

South Asian (SAS) AF: 0.424 AC: 2043 AN: 4816

European-Finnish (FIN) AF: 0.211 AC: 2226 AN: 10564

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20448 AN: 67940

Other (OTH) AF: 0.440 AC: 926 AN: 2106

Alfa AF: 0.354 Hom.: 36303

Bravo AF: 0.469

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.63
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs261532; hg19: chr5-138949362;