rs752424863

Variant names:

• chr2-159259824-T-A
• NM_001128212.3:c.790A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-159259824-T-A
• chr2-159259824-T-C

Variant summary

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

The NM_001128212.3(WDSUB1):​c.790A>T​(p.Ile264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I264V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 rank	MANE	Protein	UniProt
WDSUB1	NM_001128212.3	c.790A>T	p.Ile264Leu	missense_variant	Exon 6 of 11	ENST00000359774.9	NP_001121684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDSUB1	ENST00000359774.9	c.790A>T	p.Ile264Leu	missense_variant	Exon 6 of 11	5	NM_001128212.3	ENSP00000352820.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376850 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681730

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	.;.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.0010	.;.;.;B
Vest4		0.30
MutPred		0.54		Loss of methylation at K261 (P = 0.0626);Loss of methylation at K261 (P = 0.0626);Loss of methylation at K261 (P = 0.0626);Loss of methylation at K261 (P = 0.0626);
MVP		0.48
MPC		0.13
ClinPred		0.69	D
GERP RS		4.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: -14

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: chr2-160116335;