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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR55	NM_017706.5 link	c.629C>T	p.Ser210Phe	missense_variant	Exon 5 of 7	ENST00000358337.10	NP_060176.3	Q9H6Y2-1
WDR55	XM_005268469.4 link	c.629C>T	p.Ser210Phe	missense_variant	Exon 5 of 8		XP_005268526.1	Q9H6Y2-1
WDR55	XM_017009600.3 link	c.146C>T	p.Ser49Phe	missense_variant	Exon 6 of 8		XP_016865089.1	G3V1J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR55	ENST00000358337.10 link	c.629C>T	p.Ser210Phe	missense_variant	Exon 5 of 7	1	NM_017706.5	ENSP00000351100.5		Q9H6Y2-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over