chr12-118042862-T-C

Variant summary

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

The NM_018639.5(WSB2):ā€‹c.538A>Gā€‹(p.Ile180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

WSB2
NM_018639.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
Variant links:
Genes affected
WSB2 (HGNC:19222): (WD repeat and SOCS box containing 2) This gene encodes a member of the WD-protein subfamily. The encoded protein contains five WD-repeats spanning most of the protein and an SOCS box in the C-terminus. The SOCS box may act as a bridge between specific substrate-binding domains and E3 ubiquitin protein ligases. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

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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=0.16219032).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WSB2NM_018639.5 linkuse as main transcriptc.538A>G p.Ile180Val missense_variant 4/9 ENST00000315436.8
WSB2NM_001278557.1 linkuse as main transcriptc.589A>G p.Ile197Val missense_variant 4/9
WSB2NM_001278558.2 linkuse as main transcriptc.-71-4474A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WSB2ENST00000315436.8 linkuse as main transcriptc.538A>G p.Ile180Val missense_variant 4/91 NM_018639.5 P4Q9NYS7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251412
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461890
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00000638
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 10, 2023The c.538A>G (p.I180V) alteration is located in exon 4 (coding exon 4) of the WSB2 gene. This alteration results from a A to G substitution at nucleotide position 538, causing the isoleucine (I) at amino acid position 180 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
0.099
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Benign
0.73
DEOGEN2
Benign
0.0079
T;.;.;.
Eigen
Benign
-0.16
Eigen_PC
Benign
0.052
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.41
N;.;.;.
MutationTaster
Benign
0.99
D;D;D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.11
N;N;N;N
REVEL
Benign
0.074
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;.
Polyphen
0.36
B;.;.;.
Vest4
0.26
MutPred
0.58
Gain of catalytic residue at K176 (P = 0.0349);.;.;.;
MVP
0.17
MPC
0.52
ClinPred
0.13
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.041
gMVP
0.13

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs536208650; hg19: chr12-118480667; API