Variant chr12-118042916-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018639.5(WSB2):c.484A>G(p.Thr162Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,614,104 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 77 hom. )

Consequence

WSB2
NM_018639.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.28

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031873882).

BP6

Variant 12-118042916-T-C is Benign according to our data. Variant chr12-118042916-T-C is described in ClinVar as [Benign]. Clinvar id is 776754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WSB2	NM_018639.5 linkuse as main transcript	c.484A>G	p.Thr162Ala	missense_variant	4/9	ENST00000315436.8
WSB2	NM_001278557.1 linkuse as main transcript	c.535A>G	p.Thr179Ala	missense_variant	4/9
WSB2	NM_001278558.2 linkuse as main transcript	c.-71-4528A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSB2	ENST00000315436.8 linkuse as main transcript	c.484A>G	p.Thr162Ala	missense_variant	4/9	1	NM_018639.5	P4	Q9NYS7-1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2597

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00455

AC:

1143

AN:

251474

Hom.:

AF XY:

0.00347

AC XY:

471

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0599

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.000105

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00178

AC:

2603

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1119

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0620

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.0171

AC:

2601

AN:

152218

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1219

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00894

Hom.:

Bravo

AF:

0.0194

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0595

AC:

262

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00562

AC:

683

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.0037

T;.;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.0099

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.62

T;T;T;T

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.055

N;.;.;.

MutationTaster

Benign

1.0

D;D;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.1

N;N;N;N

REVEL

Benign

0.098

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

B;.;.;.

Vest4

0.22

MVP

0.043

MPC

0.60

ClinPred

0.029

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.027

gMVP

0.25

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