12-118043202-C-T

Position:

• chr12-118043202-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

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]

ACMG classification

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/exons	MANE	UniProt
WSB2	NM_018639.5	c.358G>A	p.Asp120Asn	missense_variant	3/9	ENST00000315436.8
WSB2	NM_001278557.1	c.409G>A	p.Asp137Asn	missense_variant	3/9
WSB2	NM_001278558.2	c.-71-4814G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WSB2	ENST00000315436.8	c.358G>A	p.Asp120Asn	missense_variant	3/9	1	NM_018639.5	P4

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 499 AN: 152222 Hom.: 1 Cov.: 32

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.: 5 AF XY: 0.00410 AC XY: 557 AN XY: 135794

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.: 28 Cov.: 32 AF XY: 0.00405 AC XY: 2948 AN XY: 727248

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.: 1 Cov.: 32 AF XY: 0.00313 AC XY: 233 AN XY: 74504

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.: 2

Bravo AF: 0.00332

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00382 AC: 464

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00769

EpiControl AF: 0.00901

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T;.;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.0038	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.50	T
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	T
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

Other links and lift over

dbSNP: rs113350351; hg19: chr12-118481007; COSMIC: COSV59573495; COSMIC: COSV59573495;