NM_018639.5:c.236G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3107675).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018639.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSB2	NM_018639.5	MANE Select	c.236G>A	p.Gly79Glu	missense	Exon 3 of 9	NP_061109.1	Q9NYS7-1
	WSB2	NM_001278557.1		c.287G>A	p.Gly96Glu	missense	Exon 3 of 9	NP_001265486.1	Q9NYS7-2
	WSB2	NM_001278558.2		c.-71-4936G>A		intron	N/A	NP_001265487.1	Q9NYS7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WSB2	ENST00000315436.8	TSL:1 MANE Select	c.236G>A	p.Gly79Glu	missense	Exon 3 of 9	ENSP00000319474.3	Q9NYS7-1
	WSB2	ENST00000535496.5	TSL:1	c.242G>A	p.Gly81Glu	missense	Exon 2 of 8	ENSP00000439450.1	F5H280
	WSB2	ENST00000540129.5	TSL:1	n.277G>A		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.19
Sift	Benign	0.12	T
Sift4G	Benign	0.24	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
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr12-118481129;