rs1557084306
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001029896.2(WDR45):c.317T>C(p.Leu106Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
WDR45
NM_001029896.2 missense
NM_001029896.2 missense
Scores
8
4
4
Clinical Significance
Conservation
PhyloP100: 8.66
Genes affected
WDR45 (HGNC:28912): (WD repeat domain 45) 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. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.916
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR45 | NM_001029896.2 | c.317T>C | p.Leu106Pro | missense_variant | 5/11 | ENST00000376372.9 | |
WDR45 | NM_007075.4 | c.320T>C | p.Leu107Pro | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR45 | ENST00000376372.9 | c.317T>C | p.Leu106Pro | missense_variant | 5/11 | 1 | NM_001029896.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodegeneration with brain iron accumulation 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerate"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with WDR45-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 107 of the WDR45 protein (p.Leu107Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.;.;T;.;T;T;T;.;T;T;.;.;T;T
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;.;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D;D;D;D;D;.;.;D;.;D;.;.;D;D;.
REVEL
Pathogenic
Sift
Benign
T;.;.;T;T;T;T;T;.;.;T;.;T;.;.;T;D;.
Sift4G
Benign
T;T;T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.
Polyphen
D;D;.;D;D;D;D;D;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0223);Gain of disorder (P = 0.0223);Gain of disorder (P = 0.0223);Gain of disorder (P = 0.0223);.;.;Gain of disorder (P = 0.0223);.;.;.;.;Gain of disorder (P = 0.0223);.;.;Gain of disorder (P = 0.0223);.;Gain of disorder (P = 0.0223);.;
MVP
MPC
2.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at