Genetic Variant WDR55:p.Ser210Phe (chr5-140668959-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017706.5(WDR55):c.629C>T(p.Ser210Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,614,056 control chromosomes in the GnomAD database, including 42,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3342 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39330 hom. )

Consequence

WDR55
NM_017706.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

44 publications found

Variant links:

Genes affected

WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

WDR55 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019042492).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017706.5. 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
	WDR55	NM_017706.5	MANE Select	c.629C>T	p.Ser210Phe	missense	Exon 5 of 7	NP_060176.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WDR55	ENST00000358337.10	TSL:1 MANE Select	c.629C>T	p.Ser210Phe	missense	Exon 5 of 7	ENSP00000351100.5
WDR55	ENST00000504897.2	TSL:2	n.146C>T		non_coding_transcript_exon	Exon 4 of 8	ENSP00000439719.1
WDR55	ENST00000506393.5	TSL:2	n.*295C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000426304.1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29320

AN:

152088

Hom.:

3326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.207

GnomAD2 exomes

AF:

0.237

AC:

59619

AN:

251404

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.239

GnomAD4 exome

AF:

0.229

AC:

334992

AN:

1461850

Hom.:

39330

Cov.:

AF XY:

0.231

AC XY:

167651

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0748

AC:

2505

AN:

33480

American (AMR)

AF:

0.247

AC:

11035

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5413

AN:

26136

East Asian (EAS)

AF:

0.296

AC:

11756

AN:

39700

South Asian (SAS)

AF:

0.252

AC:

21756

AN:

86258

European-Finnish (FIN)

AF:

0.272

AC:

14549

AN:

53412

Middle Eastern (MID)

AF:

0.216

AC:

1248

AN:

5768

European-Non Finnish (NFE)

AF:

0.227

AC:

252897

AN:

1111978

Other (OTH)

AF:

0.229

AC:

13833

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16732

33464

50197

66929

83661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8622

17244

25866

34488

43110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.193

AC:

29345

AN:

152206

Hom.:

3342

Cov.:

AF XY:

0.194

AC XY:

14468

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0783

AC:

3254

AN:

41550

American (AMR)

AF:

0.232

AC:

3540

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

735

AN:

3472

East Asian (EAS)

AF:

0.303

AC:

1569

AN:

5174

South Asian (SAS)

AF:

0.253

AC:

1219

AN:

4824

European-Finnish (FIN)

AF:

0.261

AC:

2760

AN:

10588

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15731

AN:

67994

Other (OTH)

AF:

0.212

AC:

447

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1201

2402

3603

4804

6005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

17079

Bravo

AF:

0.183

TwinsUK

AF:

0.219

AC:

811

ALSPAC

AF:

0.225

AC:

866

ESP6500AA

AF:

0.0763

AC:

336

ESP6500EA

AF:

0.234

AC:

2014

ExAC

AF:

0.236

AC:

28601

Asia WGS

AF:

0.319

AC:

1108

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

1.3

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.050

Sift

Uncertain

0.017

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.16

MPC

0.70

ClinPred

0.019

GERP RS

3.5

Varity_R

0.12

gMVP

0.32

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over