chr12-118043202-C-G

Variant names:

• chr12-118043202-C-G
• rs113350351
• NM_018639.5:c.358G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018639.5(WSB2):​c.358G>C​(p.Asp120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: WSB2 NM_018639.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31951392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WSB2	NM_018639.5	c.358G>C	p.Asp120His	missense_variant	Exon 3 of 9	ENST00000315436.8	NP_061109.1
WSB2	NM_001278557.1	c.409G>C	p.Asp137His	missense_variant	Exon 3 of 9		NP_001265486.1
WSB2	NM_001278558.2	c.-71-4814G>C		intron_variant	Intron 2 of 6		NP_001265487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WSB2	ENST00000315436.8	c.358G>C	p.Asp120His	missense_variant	Exon 3 of 9	1	NM_018639.5	ENSP00000319474.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.86	D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.042	D;D;D;T
Sift4G	Benign	0.075	T;T;T;.
Polyphen		0.81	P;.;.;.
Vest4		0.47
MutPred		0.56		Gain of catalytic residue at Q117 (P = 0);.;.;.;
MVP		0.59
MPC		1.5
ClinPred		0.67	D
GERP RS		5.1
Varity_R		0.062
gMVP		0.45

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;