2-159256370-G-T

Variant names:

• chr2-159256370-G-T
• rs7591849
• NM_001128212.3:c.958C>A

Variant summary

Our verdict is Benign. The variant received -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. 15/19 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. R320C) has been classified as Uncertain significance.

• 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
• Publications: 48 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: Benign. The variant received -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.

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.958C>A	p.Arg320Ser	missense	Exon 9 of 11	NP_001121684.1	Q8N9V3-1
	WDSUB1	NM_001128213.2		c.958C>A	p.Arg320Ser	missense	Exon 9 of 11	NP_001121685.1	Q8N9V3-1
	WDSUB1	NM_001330278.2		c.958C>A	p.Arg320Ser	missense	Exon 9 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.958C>A	p.Arg320Ser	missense	Exon 9 of 11	ENSP00000352820.4	Q8N9V3-1
	WDSUB1	ENST00000358147.8	TSL:1	c.682C>A	p.Arg228Ser	missense	Exon 5 of 7	ENSP00000350866.4	Q8N9V3-2
	WDSUB1	ENST00000851154.1		c.958C>A	p.Arg320Ser	missense	Exon 9 of 12	ENSP00000521213.1

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

GnomAD2 exomes AF: 0.492 AC: 120239 AN: 244576 AF XY: 0.492

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 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

African (AFR) AF: 0.724 AC: 24014 AN: 33182

American (AMR) AF: 0.338 AC: 14612 AN: 43282

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 16279 AN: 26040

East Asian (EAS) AF: 0.271 AC: 10715 AN: 39520

South Asian (SAS) AF: 0.390 AC: 32858 AN: 84304

European-Finnish (FIN) AF: 0.390 AC: 20823 AN: 53350

Middle Eastern (MID) AF: 0.514 AC: 2952 AN: 5748

European-Non Finnish (NFE) AF: 0.581 AC: 643516 AN: 1108434

Other (OTH) AF: 0.535 AC: 32203 AN: 60174

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

African (AFR) AF: 0.716 AC: 29711 AN: 41486

American (AMR) AF: 0.434 AC: 6616 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2197 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1359 AN: 5178

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4824

European-Finnish (FIN) AF: 0.365 AC: 3846 AN: 10546

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39454 AN: 67974

Other (OTH) AF: 0.572 AC: 1204 AN: 2106

Alfa AF: 0.571 Hom.: 89111

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 v4.9

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
MetaRNN	Benign	0.0000030	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.068
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.096
Sift	Benign	0.78	T
Sift4G	Benign	0.74	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
Mutation Taster		=95/5	polymorphism (auto)

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