12-118043324-C-T

Variant names:

• chr12-118043324-C-T
• NM_018639.5:c.236G>A

Variant summary

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

The NM_018639.5(WSB2):​c.236G>A​(p.Gly79Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WSB2 NM_018639.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

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=0.3107675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WSB2	NM_018639.5	c.236G>A	p.Gly79Glu	missense_variant	Exon 3 of 9	ENST00000315436.8	NP_061109.1
WSB2	NM_001278557.1	c.287G>A	p.Gly96Glu	missense_variant	Exon 3 of 9		NP_001265486.1
WSB2	NM_001278558.2	c.-71-4936G>A		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.236G>A	p.Gly79Glu	missense_variant	Exon 3 of 9	1	NM_018639.5	ENSP00000319474.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236G>A (p.G79E) alteration is located in exon 3 (coding exon 3) of the WSB2 gene. This alteration results from a G to A substitution at nucleotide position 236, causing the glycine (G) at amino acid position 79 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.0	N;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.92	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.24	T;D;T;.
Polyphen		1.0	D;.;.;.
Vest4		0.45
MutPred		0.42		Gain of loop (P = 0.0097);.;.;.;
MVP		0.40
MPC		0.94
ClinPred		0.49	T
GERP RS		5.2
Varity_R		0.14
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-118481129;