rs369953265

Variant summary

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

The NM_024100.4(WDR18):​c.448C>G​(p.Leu150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign 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. L150F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

WDR18
NM_024100.4 missense

Scores

4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40
Variant links:
Genes affected
WDR18 (HGNC:17956): (WD repeat domain 18) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

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=0.22275415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR18NM_024100.4 linkc.448C>G p.Leu150Val missense_variant Exon 3 of 10 ENST00000585809.6 NP_077005.2 Q9BV38
WDR18NM_001372085.1 linkc.448C>G p.Leu150Val missense_variant Exon 5 of 12 NP_001359014.1
WDR18NM_001372086.1 linkc.217C>G p.Leu73Val missense_variant Exon 6 of 13 NP_001359015.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR18ENST00000585809.6 linkc.448C>G p.Leu150Val missense_variant Exon 3 of 10 1 NM_024100.4 ENSP00000476117.3 Q9BV38

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000408
AC:
1
AN:
245082
Hom.:
0
AF XY:
0.00000753
AC XY:
1
AN XY:
132844
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:
0.0000334
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1456206
Hom.:
0
Cov.:
32
AF XY:
0.00000414
AC XY:
3
AN XY:
724186
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:
0.0000467
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.
Eigen
Benign
-0.073
Eigen_PC
Benign
-0.069
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;.
PrimateAI
Benign
0.41
T
Sift4G
Benign
0.30
T;T;D
Polyphen
0.70
P;.;.
Vest4
0.38
MutPred
0.43
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;
MVP
0.068
ClinPred
0.55
D
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.36

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: rs369953265; hg19: chr19-989888; API