2-159256220-T-G

Position:

• chr2-159256220-T-G

Variant summary

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

The NM_001128212.3(WDSUB1):​c.1108A>C​(p.Ser370Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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	UniProt
WDSUB1	NM_001128212.3	c.1108A>C	p.Ser370Arg	missense_variant	9/11	ENST00000359774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDSUB1	ENST00000359774.9	c.1108A>C	p.Ser370Arg	missense_variant	9/11	5	NM_001128212.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jan 03, 2024

The c.1108A>C (p.S370R) alteration is located in exon 9 (coding exon 8) of the WDSUB1 gene. This alteration results from a A to C substitution at nucleotide position 1108, causing the serine (S) at amino acid position 370 to be replaced by an arginine (R). 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	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	.;.;.;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	.;.;.;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.43	T;T;T;T;T
MetaSVM	Uncertain	0.43	D
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.057	T;D;T;T;T
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.98	.;.;.;.;D
Vest4		0.39
MutPred		0.49		Loss of phosphorylation at S370 (P = 0.0521);.;Loss of phosphorylation at S370 (P = 0.0521);Loss of phosphorylation at S370 (P = 0.0521);Loss of phosphorylation at S370 (P = 0.0521);
MVP		0.89
MPC		0.44
ClinPred		0.96	D
GERP RS		5.8
gMVP		0.47

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: chr2-160112731;