dbSNP rs139082900: WDR55:p.Pro32Arg (chr5-140665007-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017706.5(WDR55):c.95C>G(p.Pro32Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P32L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WDR55
NM_017706.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.61

Publications

0 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:

LOC124901088 (HGNC:):

LOC124901088 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.78

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.95C>G	p.Pro32Arg	missense	Exon 1 of 7	NP_060176.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR55	ENST00000358337.10	TSL:1 MANE Select	c.95C>G	p.Pro32Arg	missense	Exon 1 of 7	ENSP00000351100.5	Q9H6Y2-1
	WDR55	ENST00000506393.5	TSL:2	n.95C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000426304.1	D6RGJ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249442

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000671

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111878

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

PhyloP100

5.6

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.73

MutPred

0.45

Loss of loop (P = 0.1258)

MVP

0.54

MPC

0.96

ClinPred

0.99

GERP RS

5.2

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.85

gMVP

0.57

Mutation Taster

=34/66

disease causing

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over