17-1725291-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163809.2(WDR81):​c.332G>C​(p.Arg111Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

WDR81
NM_001163809.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63
Variant links:
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
WDR81NM_001163809.2 linkuse as main transcriptc.332G>C p.Arg111Pro missense_variant 1/10 ENST00000409644.6 NP_001157281.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR81ENST00000409644.6 linkuse as main transcriptc.332G>C p.Arg111Pro missense_variant 1/101 NM_001163809.2 ENSP00000386609 P1Q562E7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
76
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsNov 15, 2023The c.332G>C (p.R111P) alteration is located in exon 1 (coding exon 1) of the WDR81 gene. This alteration results from a G to C substitution at nucleotide position 332, causing the arginine (R) at amino acid position 111 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.050
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.059
D
MetaRNN
Uncertain
0.42
T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
0.96
D;D;D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.12
Sift
Benign
0.21
T
Sift4G
Benign
0.069
T
Vest4
0.62
MutPred
0.36
Loss of MoRF binding (P = 0.0072);
MVP
0.61
MPC
1.1
ClinPred
0.86
D
GERP RS
3.9
Varity_R
0.38
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1628585; API