chr17-1725165-G-T
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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):c.206G>T(p.Arg69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000652 in 1,533,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000058 ( 0 hom. )
Consequence
WDR81
NM_001163809.2 missense
NM_001163809.2 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 2.71
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.206G>T | p.Arg69Leu | 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.206G>T | p.Arg69Leu | missense_variant | 1/10 | 1 | NM_001163809.2 | ENSP00000386609 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000379 AC: 5AN: 131834Hom.: 0 AF XY: 0.0000139 AC XY: 1AN XY: 71820
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GnomAD4 exome AF: 0.00000579 AC: 8AN: 1381620Hom.: 0 Cov.: 76 AF XY: 0.00000440 AC XY: 3AN XY: 681322
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74512
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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 | Jul 09, 2021 | The c.206G>T (p.R69L) alteration is located in exon 1 (coding exon 1) of the WDR81 gene. This alteration results from a G to T substitution at nucleotide position 206, causing the arginine (R) at amino acid position 69 to be replaced by a leucine (L). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MutPred
Loss of disorder (P = 0.0409);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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