12-118043322-G-C

Variant names:

• chr12-118043322-G-C
• NM_018639.5:c.238C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018639.5(WSB2):​c.238C>G​(p.Arg80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 (0 hom.)
• Consequence: WSB2 NM_018639.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23368677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WSB2	NM_018639.5	c.238C>G	p.Arg80Gly	missense_variant	Exon 3 of 9	ENST00000315436.8	NP_061109.1
WSB2	NM_001278557.1	c.289C>G	p.Arg97Gly	missense_variant	Exon 3 of 9		NP_001265486.1
WSB2	NM_001278558.2	c.-71-4934C>G		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.238C>G	p.Arg80Gly	missense_variant	Exon 3 of 9	1	NM_018639.5	ENSP00000319474.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1451026 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 720924

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: 0.00000271

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	0.082
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	T;.;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.60	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.046	D;D;D;D
Sift4G	Benign	0.35	T;T;T;.
Polyphen		0.96	D;.;.;.
Vest4		0.46
MutPred		0.47		Gain of sheet (P = 0.0149);.;.;.;
MVP		0.10
MPC		0.79
ClinPred		0.49	T
GERP RS		5.2
Varity_R		0.11
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-118481127;