chr14-102208994-A-G

Variant summary

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

The NM_144574.4(WDR20):ā€‹c.824A>Gā€‹(p.Lys275Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

WDR20
NM_144574.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15
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=0.20588803).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR20NM_144574.4 linkuse as main transcriptc.824A>G p.Lys275Arg 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.824A>G p.Lys275Arg missense_variant 3/31 NM_144574.4 ENSP00000341037 Q8TBZ3-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727248
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMar 06, 2023The c.917A>G (p.K306R) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a A to G substitution at nucleotide position 917, causing the lysine (K) at amino acid position 306 to be replaced by an arginine (R). 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
Benign
0.077
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Benign
19
DANN
Benign
0.64
DEOGEN2
Benign
0.13
.;.;T;.;.;.
Eigen
Benign
-0.045
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T;T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.21
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.48
N;.;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
0.26
N;.;N;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.79
T;.;T;T;T;T
Sift4G
Benign
0.58
T;T;T;T;T;T
Polyphen
0.0080
B;.;B;.;.;.
Vest4
0.42
MutPred
0.52
Gain of catalytic residue at S271 (P = 0);.;Gain of catalytic residue at S271 (P = 0);.;.;.;
MVP
0.65
MPC
0.42
ClinPred
0.25
T
GERP RS
5.8
Varity_R
0.16
gMVP
0.37

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: rs768943158; hg19: chr14-102675331; API