chr2-159279832-C-T

Variant names:

• chr2-159279832-C-T
• rs2061615425
• NM_001128212.3:c.512G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128212.3(WDSUB1):​c.512G>A​(p.Arg171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15253913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128212.3. 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
	WDSUB1	NM_001128212.3	MANE Select	c.512G>A	p.Arg171Lys	missense	Exon 3 of 11	NP_001121684.1	Q8N9V3-1
	WDSUB1	NM_001128213.2		c.512G>A	p.Arg171Lys	missense	Exon 3 of 11	NP_001121685.1	Q8N9V3-1
	WDSUB1	NM_001330278.2		c.512G>A	p.Arg171Lys	missense	Exon 3 of 11	NP_001317207.1	Q8N9V3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDSUB1	ENST00000359774.9	TSL:5 MANE Select	c.512G>A	p.Arg171Lys	missense	Exon 3 of 11	ENSP00000352820.4	Q8N9V3-1
	WDSUB1	ENST00000358147.8	TSL:1	c.512G>A	p.Arg171Lys	missense	Exon 3 of 7	ENSP00000350866.4	Q8N9V3-2
	WDSUB1	ENST00000851154.1		c.512G>A	p.Arg171Lys	missense	Exon 3 of 12	ENSP00000521213.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.090
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.10
Sift	Benign	0.47	T
Sift4G	Benign	0.90	T
Polyphen		0.62	P
Vest4		0.14
MutPred		0.37		Gain of ubiquitination at R171 (P = 0.0146)
MVP		0.72
MPC		0.10
ClinPred		0.42	T
GERP RS		5.8
gMVP		0.43
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs2061615425; hg19: chr2-160136343;