14-100468093-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001161476.3(WDR25):​c.895C>T​(p.Arg299Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,613,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

WDR25
NM_001161476.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69
Variant links:
Genes affected
WDR25 (HGNC:21064): (WD repeat domain 25) This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2959473).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR25NM_001161476.3 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant 3/7 ENST00000402312.8 NP_001154948.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR25ENST00000402312.8 linkuse as main transcriptc.895C>T p.Arg299Trp missense_variant 3/72 NM_001161476.3 ENSP00000385540 P1Q64LD2-1

Frequencies

GnomAD3 genomes
AF:
0.000302
AC:
46
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00150
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:
0.000294
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
250716
Hom.:
0
AF XY:
0.000243
AC XY:
33
AN XY:
135544
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000235
AC:
344
AN:
1461226
Hom.:
0
Cov.:
31
AF XY:
0.000250
AC XY:
182
AN XY:
726944
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000263
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000302
AC:
46
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.000959
Alfa
AF:
0.000267
Hom.:
0
Bravo
AF:
0.000298
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000181
AC:
22
EpiCase
AF:
0.000382
EpiControl
AF:
0.000178

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 GeneticsNov 14, 2023The c.895C>T (p.R299W) alteration is located in exon 3 (coding exon 2) of the WDR25 gene. This alteration results from a C to T substitution at nucleotide position 895, causing the arginine (R) at amino acid position 299 to be replaced by a tryptophan (W). 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
0.14
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;T;T;.
Eigen
Benign
-0.030
Eigen_PC
Benign
-0.013
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.95
.;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.30
T;T;T;T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
1.4
L;L;L;.
MutationTaster
Benign
0.71
D;D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-4.0
D;D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.011
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.060
B;B;B;D
Vest4
0.67
MVP
0.45
MPC
0.34
ClinPred
0.18
T
GERP RS
4.1
Varity_R
0.18
gMVP
0.47

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: rs199801334; hg19: chr14-100934430; API