Variant chr12-118043202-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018639.5(WSB2):c.358G>A(p.Asp120Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,614,234 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 28 hom. )

Consequence

WSB2
NM_018639.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.89

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]

WSB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037802756).

BP6

Variant 12-118043202-C-T is Benign according to our data. Variant chr12-118043202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00396 (5792/1461894) while in subpopulation MID AF= 0.0182 (105/5768). AF 95% confidence interval is 0.0154. There are 28 homozygotes in gnomad4_exome. There are 2948 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WSB2	NM_018639.5 link	c.358G>A	p.Asp120Asn	missense_variant	Exon 3 of 9	ENST00000315436.8	NP_061109.1	Q9NYS7-1
WSB2	NM_001278557.1 link	c.409G>A	p.Asp137Asn	missense_variant	Exon 3 of 9		NP_001265486.1	Q9NYS7-2
WSB2	NM_001278558.2 link	c.-71-4814G>A		intron_variant	Intron 2 of 6		NP_001265487.1	Q9NYS7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WSB2	ENST00000315436.8 link	c.358G>A	p.Asp120Asn	missense_variant	Exon 3 of 9	1	NM_018639.5	ENSP00000319474.3		Q9NYS7-1

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

499

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00358

AC:

900

AN:

251218

Hom.:

AF XY:

0.00410

AC XY:

557

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00559

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00396

AC:

5792

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

2948

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00464

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00434

Gnomad4 OTH exome

AF:

0.00435

GnomAD4 genome

AF:

0.00326

AC:

496

AN:

152340

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00332

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00382

AC:

464

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00901

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

WSB2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0040

T;.;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.16

N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.49

T;T;T;.

Polyphen

0.0010

B;.;.;.

Vest4

0.23

MVP

0.10

MPC

0.60

ClinPred

0.027

GERP RS

5.1

Varity_R

0.045

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over