2-159256370-G-T

Position:

• chr2-159256370-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128212.3(WDSUB1):​c.958C>A​(p.Arg320Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,606,078 control chromosomes in the GnomAD database, including 251,696 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.57 (26167 hom., cov: 33)
  • Exomes 𝑓: 0.55 (225529 hom.)
• Consequence: WDSUB1 NM_001128212.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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]

WDSUB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9788073E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDSUB1	NM_001128212.3	c.958C>A	p.Arg320Ser	missense_variant	9/11	ENST00000359774.9	NP_001121684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDSUB1	ENST00000359774.9	c.958C>A	p.Arg320Ser	missense_variant	9/11	5	NM_001128212.3	ENSP00000352820.4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86867 AN: 151926 Hom.: 26148 Cov.: 33

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.572

GnomAD3 exomes AF: 0.492 AC: 120239 AN: 244576 Hom.: 32050 AF XY: 0.492 AC XY: 64932 AN XY: 131972

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.581

Gnomad OTH exome AF: 0.513

GnomAD4 exome AF: 0.549 AC: 797972 AN: 1454034 Hom.: 225529 Cov.: 40 AF XY: 0.544 AC XY: 393579 AN XY: 723002

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.572 AC: 86920 AN: 152044 Hom.: 26167 Cov.: 33 AF XY: 0.551 AC XY: 40950 AN XY: 74326

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.572

Alfa AF: 0.566 Hom.: 58072

Bravo AF: 0.583

TwinsUK AF: 0.575 AC: 2133

ALSPAC AF: 0.587 AC: 2262

ESP6500AA AF: 0.718 AC: 3163

ESP6500EA AF: 0.573 AC: 4931

ExAC AF: 0.504 AC: 61211

Asia WGS AF: 0.346 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.0039	.;.;.;.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.099	.;.;.;T;T
MetaRNN	Benign	0.0000030	T;T;T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.61	N;N;N;N;N
REVEL	Benign	0.096
Sift	Benign	0.78	T;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T
Polyphen		0.0	.;.;.;.;B
Vest4		0.049
MPC		0.085
ClinPred		0.0029	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.28

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: rs7591849; hg19: chr2-160112881; COSMIC: COSV63067087;