5-139564848-T-C

Variant names:

• chr5-139564848-T-C
• rs769052
• NM_003339.3:c.24+3033T>C

Variant summary

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

The NM_003339.3(UBE2D2):​c.24+3033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 152,274 control chromosomes in the GnomAD database, including 956 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 0.097 (956 hom., cov: 32)
• Consequence: UBE2D2 NM_003339.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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

Verdict is Benign. Variant got -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 = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2D2	NM_003339.3	c.24+3033T>C		intron_variant	Intron 1 of 6	ENST00000398733.8	NP_003330.1
UBE2D2	NM_181838.2	c.-64+2441T>C		intron_variant	Intron 2 of 7		NP_862821.1
UBE2D2	XM_047417691.1	c.-63-35524T>C		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+3033T>C		intron_variant	Intron 1 of 6	1	NM_003339.3	ENSP00000381717.3

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14662 AN: 152156 Hom.: 942 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0966 AC: 14707 AN: 152274 Hom.: 956 Cov.: 32 AF XY: 0.0943 AC XY: 7019 AN XY: 74466

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0765 Hom.: 250

Bravo AF: 0.102

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.71

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: rs769052; hg19: chr5-138944433;