chr17-1725204-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001163809.2(WDR81):āc.245T>Cā(p.Leu82Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,538,186 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 1 hom. )
Consequence
WDR81
NM_001163809.2 missense
NM_001163809.2 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.16
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR81 | NM_001163809.2 | c.245T>C | p.Leu82Pro | missense_variant | 1/10 | ENST00000409644.6 | NP_001157281.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR81 | ENST00000409644.6 | c.245T>C | p.Leu82Pro | missense_variant | 1/10 | 1 | NM_001163809.2 | ENSP00000386609 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152216Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000160 AC: 22AN: 137548Hom.: 0 AF XY: 0.000134 AC XY: 10AN XY: 74756
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GnomAD4 exome AF: 0.000162 AC: 224AN: 1385970Hom.: 1 Cov.: 77 AF XY: 0.000152 AC XY: 104AN XY: 684040
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | The c.245T>C (p.L82P) alteration is located in exon 1 (coding exon 1) of the WDR81 gene. This alteration results from a T to C substitution at nucleotide position 245, causing the leucine (L) at amino acid position 82 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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