Genetic Variant NM_018299.6:c.214A>G (chr8-73810626-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018299.6(UBE2W):c.214A>G(p.Met72Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBE2W
NM_018299.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

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]

UBE2W links:

ENSG00000258677 (HGNC:):

ENSG00000258677 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23053855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2W	NM_018299.6 link	c.214A>G	p.Met72Val	missense_variant	Exon 4 of 6	ENST00000602593.6	NP_060769.5	Q96B02-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2W	ENST00000602593.6 link	c.214A>G	p.Met72Val	missense_variant	Exon 4 of 6	1	NM_018299.6	ENSP00000473561.1		Q96B02-1
ENSG00000258677	ENST00000358757.5 link	n.214A>G		non_coding_transcript_exon_variant	Exon 4 of 8	4		ENSP00000454445.2		H3BMM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719518

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247A>G (p.M83V) alteration is located in exon 5 (coding exon 5) of the UBE2W gene. This alteration results from a A to G substitution at nucleotide position 247, causing the methionine (M) at amino acid position 83 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.045

.;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.95

.;N;.

PrimateAI

Uncertain

0.75

REVEL

Benign

0.10

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.27

MutPred

0.34

.;Gain of phosphorylation at T74 (P = 0.1441);.;

MVP

0.043

MPC

0.65

ClinPred

0.26

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over