chr2-159279832-C-T

Position:

• chr2-159279832-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/19 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDSUB1	NM_001128212.3	c.512G>A	p.Arg171Lys	missense_variant	3/11	ENST00000359774.9	NP_001121684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDSUB1	ENST00000359774.9	c.512G>A	p.Arg171Lys	missense_variant	3/11	5	NM_001128212.3	ENSP00000352820.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 12, 2024

The c.512G>A (p.R171K) alteration is located in exon 3 (coding exon 2) of the WDSUB1 gene. This alteration results from a G to A substitution at nucleotide position 512, causing the arginine (R) at amino acid position 171 to be replaced by a lysine (K). 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	0.090
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;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.17	N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.47	T;T;T;T;T
Sift4G	Benign	0.90	T;T;T;T;T
Polyphen		0.62	.;.;.;.;P
Vest4		0.14
MutPred		0.37		Gain of ubiquitination at R171 (P = 0.0146);Gain of ubiquitination at R171 (P = 0.0146);Gain of ubiquitination at R171 (P = 0.0146);Gain of ubiquitination at R171 (P = 0.0146);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

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

LitVar

Other links and lift over

dbSNP: rs2061615425; hg19: chr2-160136343;