chr8-73810557-G-C

Variant names:

• chr8-73810557-G-C
• NM_018299.6:c.283C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018299.6(UBE2W):​c.283C>G​(p.Leu95Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2W NM_018299.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

Genes affected

UBE2W (HGNC:25616): (ubiquitin conjugating enzyme E2 W) This gene encodes a nuclear-localized ubiquitin-conjugating enzyme (E2) that, along with ubiquitin-activating (E1) and ligating (E3) enzymes, coordinates the addition of a ubiquitin moiety to existing proteins. The encoded protein promotes the ubiquitination of Fanconi anemia complementation group proteins and may be important in the repair of DNA damage. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ENSG00000258677 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018299.6. 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
	UBE2W	NM_018299.6	MANE Select	c.283C>G	p.Leu95Val	missense	Exon 4 of 6	NP_060769.5
	UBE2W	NM_001001481.4		c.316C>G	p.Leu106Val	missense	Exon 5 of 7	NP_001001481.3	Q96B02-2
	UBE2W	NM_001271015.3		c.283C>G	p.Leu95Val	missense	Exon 4 of 6	NP_001257944.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2W	ENST00000602593.6	TSL:1 MANE Select	c.283C>G	p.Leu95Val	missense	Exon 4 of 6	ENSP00000473561.1	Q96B02-1
	UBE2W	ENST00000419880.7	TSL:1	c.403C>G	p.Leu135Val	missense	Exon 5 of 7	ENSP00000397453.3	X6REH9
	UBE2W	ENST00000517608.5	TSL:1	c.370C>G	p.Leu124Val	missense	Exon 4 of 6	ENSP00000428813.2	Q96B02-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		5.0
PrimateAI	Pathogenic	0.88	D
REVEL	Uncertain	0.53
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.89		Loss of stability (P = 0.0322)
MVP		0.42
MPC		1.7
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Varity_R		0.83
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr8-74722792;