17-1725300-G-C

Variant summary

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

The NM_001163809.2(WDR81):ā€‹c.341G>Cā€‹(p.Arg114Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000038 in 1,395,580 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000038 ( 1 hom. )

Consequence

WDR81
NM_001163809.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66
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]

Genome browser will be placed here

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.341G>C p.Arg114Thr 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.341G>C p.Arg114Thr missense_variant 1/101 NM_001163809.2 ENSP00000386609 P1Q562E7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000134
AC:
2
AN:
148942
Hom.:
0
AF XY:
0.0000249
AC XY:
2
AN XY:
80176
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000717
Gnomad NFE exome
AF:
0.0000175
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000380
AC:
53
AN:
1395580
Hom.:
1
Cov.:
74
AF XY:
0.0000349
AC XY:
24
AN XY:
688396
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000252
Gnomad4 FIN exome
AF:
0.0000220
Gnomad4 NFE exome
AF:
0.0000445
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113

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 17, 2022The c.341G>C (p.R114T) 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 341, causing the arginine (R) at amino acid position 114 to be replaced by a threonine (T). 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
Uncertain
0.43
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Benign
0.91
DEOGEN2
Benign
0.022
T
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
D;D;D;D;N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.058
Sift
Benign
0.22
T
Sift4G
Uncertain
0.0080
D
Vest4
0.60
MVP
0.63
MPC
1.4
ClinPred
0.17
T
GERP RS
3.7
Varity_R
0.12
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs922125870; hg19: chr17-1628594; API