12-118043273-C-G

Variant summary

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

The NM_018639.5(WSB2):ā€‹c.287G>Cā€‹(p.Gly96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 32)
Exomes š‘“: 0.000033 ( 0 hom. )

Consequence

WSB2
NM_018639.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02
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]

Genome browser will be placed here

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=0.094718635).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WSB2NM_018639.5 linkuse as main transcriptc.287G>C p.Gly96Ala missense_variant 3/9 ENST00000315436.8
WSB2NM_001278557.1 linkuse as main transcriptc.338G>C p.Gly113Ala missense_variant 3/9
WSB2NM_001278558.2 linkuse as main transcriptc.-71-4885G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WSB2ENST00000315436.8 linkuse as main transcriptc.287G>C p.Gly96Ala missense_variant 3/91 NM_018639.5 P4Q9NYS7-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152234
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.000111
AC:
28
AN:
251176
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000665
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:
0.0000264
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.0000261
AC XY:
19
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000559
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:
0.0000144
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00192
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.000144
ExAC
AF:
0.000123
AC:
15

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 04, 2024The c.287G>C (p.G96A) alteration is located in exon 3 (coding exon 3) of the WSB2 gene. This alteration results from a G to C substitution at nucleotide position 287, causing the glycine (G) at amino acid position 96 to be replaced by an alanine (A). 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
0.24
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T;.;.;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.76
T;T;T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.095
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.31
T;T;T;T
Sift4G
Benign
0.40
T;T;T;.
Polyphen
0.98
D;.;.;.
Vest4
0.29
MutPred
0.44
Gain of catalytic residue at G91 (P = 0.0031);.;.;.;
MVP
0.082
MPC
0.88
ClinPred
0.089
T
GERP RS
5.2
Varity_R
0.10
gMVP
0.64

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: rs750304066; hg19: chr12-118481078; API