NM_003343.6:c.125+4194G>T

Variant names:

• chr21-44783726-C-A
• rs2329900
• NM_003343.6:c.125+4194G>T

Variant summary

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

The NM_003343.6(UBE2G2):​c.125+4194G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,132 control chromosomes in the GnomAD database, including 10,574 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 0.36 (10574 hom., cov: 33)
• Consequence: UBE2G2 NM_003343.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 5 publications found

Genes affected

UBE2G2 (HGNC:12483): (ubiquitin conjugating enzyme E2 G2) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein shares 100% sequence identity with the mouse counterpart. This gene is ubiquitously expressed, with high expression seen in adult muscle. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2G2	NM_003343.6	c.125+4194G>T		intron_variant	Intron 3 of 5	ENST00000345496.7	NP_003334.2
UBE2G2	NM_182688.3	c.41+4194G>T		intron_variant	Intron 4 of 6		NP_872630.1
UBE2G2	NM_001202489.2	c.-85-6309G>T		intron_variant	Intron 1 of 3		NP_001189418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2G2	ENST00000345496.7	c.125+4194G>T		intron_variant	Intron 3 of 5	1	NM_003343.6	ENSP00000338348.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55075 AN: 152014 Hom.: 10562 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.362 AC: 55120 AN: 152132 Hom.: 10574 Cov.: 33 AF XY: 0.357 AC XY: 26547 AN XY: 74364

African (AFR) AF: 0.275 AC: 11389 AN: 41484

American (AMR) AF: 0.301 AC: 4605 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1393 AN: 3470

East Asian (EAS) AF: 0.154 AC: 799 AN: 5182

South Asian (SAS) AF: 0.451 AC: 2175 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3522 AN: 10586

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29840 AN: 67972

Other (OTH) AF: 0.385 AC: 814 AN: 2112

Alfa AF: 0.407 Hom.: 32676

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
DANN	Benign	0.30
PhyloP100		-0.15
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: rs2329900; hg19: chr21-46203641;