14-102208807-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144574.4(WDR20):​c.637C>T​(p.Leu213Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,614,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

WDR20
NM_144574.4 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83
Variant links:
Genes affected
WDR20 (HGNC:19667): (WD repeat domain 20) This gene encodes a WD repeat-containing protein that functions to preserve and regulate the activity of the USP12-UAF1 deubiquitinating enzyme complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19478714).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR20NM_144574.4 linkuse as main transcriptc.637C>T p.Leu213Phe missense_variant 3/3 ENST00000342702.8 NP_653175.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR20ENST00000342702.8 linkuse as main transcriptc.637C>T p.Leu213Phe missense_variant 3/31 NM_144574.4 ENSP00000341037 Q8TBZ3-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152252
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251460
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000533
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152370
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 19, 2022The c.730C>T (p.L244F) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a C to T substitution at nucleotide position 730, causing the leucine (L) at amino acid position 244 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
.;.;D;.;.;.;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.19
T;T;T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.2
M;.;M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.2
D;.;D;D;D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0030
D;.;D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D
Polyphen
0.97
D;.;D;.;.;.;.
Vest4
0.83
MutPred
0.32
Gain of catalytic residue at L214 (P = 0);.;Gain of catalytic residue at L214 (P = 0);.;.;.;.;
MVP
0.46
MPC
1.4
ClinPred
0.34
T
GERP RS
5.5
Varity_R
0.68
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781513294; hg19: chr14-102675144; COSMIC: COSV100085175; COSMIC: COSV100085175; API