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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003343.6(UBE2G2):​c.125+4194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 152,188 control chromosomes in the GnomAD database, including 3 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 0.00049 (3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003343.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2G2	NM_003343.6	MANE Select	c.125+4194G>A		intron	N/A	NP_003334.2
	UBE2G2	NM_182688.3		c.41+4194G>A		intron	N/A	NP_872630.1	P60604-2
	UBE2G2	NM_001202489.2		c.-85-6309G>A		intron	N/A	NP_001189418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2G2	ENST00000345496.7	TSL:1 MANE Select	c.125+4194G>A		intron	N/A	ENSP00000338348.3	P60604-1
	UBE2G2	ENST00000907888.1		c.110+4194G>A		intron	N/A	ENSP00000577947.1
	UBE2G2	ENST00000914956.1		c.125+4194G>A		intron	N/A	ENSP00000585015.1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152070 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152188 Hom.: 3 Cov.: 33 AF XY: 0.000672 AC XY: 50 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 32676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.90
PhyloP100		-0.15

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;