rs2286394

chr5-140668959-C-T

Variant summary

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

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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3342 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39330 hom.)
• Consequence: WDR55 NM_017706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
WDR55	NM_017706.5	c.629C>T	p.Ser210Phe	missense_variant	5/7	ENST00000358337.10
WDR55	XM_005268469.4	c.629C>T	p.Ser210Phe	missense_variant	5/8
WDR55	XM_017009600.3	c.146C>T	p.Ser49Phe	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR55	ENST00000358337.10	c.629C>T	p.Ser210Phe	missense_variant	5/7	1	NM_017706.5	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29320 AN: 152088 Hom.: 3326 Cov.: 32

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

GnomAD3 exomes AF: 0.237 AC: 59619 AN: 251404 Hom.: 7479 AF XY: 0.239 AC XY: 32520 AN XY: 135888

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 SAS exome AF: 0.256

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.: 46 AF XY: 0.231 AC XY: 167651 AN XY: 727226

Gnomad4 AFR exome AF: 0.0748

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.193 AC: 29345 AN: 152206 Hom.: 3342 Cov.: 32 AF XY: 0.194 AC XY: 14468 AN XY: 74416

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.212

Alfa AF: 0.223 Hom.: 9629

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	T
BayesDel_noAF	Benign	-0.49
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.31	P
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.050
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.16
MPC		0.70
ClinPred		0.019	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs2286394; hg19: chr5-140048544; COSMIC: COSV56908033; COSMIC: COSV56908033;