2-159248463-C-A

Position:

• chr2-159248463-C-A

Variant summary

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

The NM_001128212.3(WDSUB1):​c.1182G>T​(p.Arg394Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.301

Genes affected

WDSUB1 (HGNC:26697): (WD repeat, sterile alpha motif and U-box domain containing 1) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDSUB1	NM_001128212.3	c.1182G>T	p.Arg394Ser	missense_variant	10/11	ENST00000359774.9	NP_001121684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDSUB1	ENST00000359774.9	c.1182G>T	p.Arg394Ser	missense_variant	10/11	5	NM_001128212.3	ENSP00000352820.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.1182G>T (p.R394S) alteration is located in exon 10 (coding exon 9) of the WDSUB1 gene. This alteration results from a G to T substitution at nucleotide position 1182, causing the arginine (R) at amino acid position 394 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.83	.;.;.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Uncertain	-0.15	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.20	T;D;T;T
Sift4G	Benign	0.14	T;D;T;T
Vest4		0.39
MutPred		0.49		Gain of phosphorylation at R394 (P = 0.0205);.;Gain of phosphorylation at R394 (P = 0.0205);Gain of phosphorylation at R394 (P = 0.0205);
MVP		0.81
MPC		0.30
ClinPred		0.96	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.53

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: chr2-160104974;