rs770279237
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001163809.2(WDR81):c.3286C>T(p.Gln1096Ter) variant causes a stop gained change. 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
WDR81
NM_001163809.2 stop_gained
NM_001163809.2 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
WDR81 (HGNC:26600): (WD repeat domain 81) This gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. Mutations in this gene are associated with an autosomal recessive form of a syndrome exhibiting cerebellar ataxia, cognitive disability, and disequilibrium (CAMRQ2). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-1728245-C-T is Pathogenic according to our data. Variant chr17-1728245-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 191291.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR81 | NM_001163809.2 | c.3286C>T | p.Gln1096Ter | stop_gained | 1/10 | ENST00000409644.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR81 | ENST00000409644.6 | c.3286C>T | p.Gln1096Ter | stop_gained | 1/10 | 1 | NM_001163809.2 | P1 | |
ENST00000576540.1 | n.296-2334G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248588Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135048
GnomAD3 exomes
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1
AN:
248588
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1
AN XY:
135048
Gnomad AFR exome
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GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
AC:
1
EpiCase
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
not provided Pathogenic:1
Likely pathogenic, flagged submission | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Hydrocephalus, congenital, 3, with brain anomalies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 10, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;D;D;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at