rs201917309

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001163673.2(WDR81):ā€‹c.51C>Gā€‹(p.Ser17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S17S) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000029 ( 0 hom. )

Consequence

WDR81
NM_001163673.2 missense

Scores

1
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.554
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]
MIR22HG (HGNC:28219): (MIR22 host gene) Predicted to act upstream of or within response to wounding. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09287542).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR81NM_001163673.2 linkc.51C>G p.Ser17Arg missense_variant Exon 1 of 10 NP_001157145.1 Q562E7-5
WDR81NM_152348.4 linkc.-131C>G 5_prime_UTR_variant Exon 1 of 11 NP_689561.2 Q562E7-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR81ENST00000446363 linkc.-397C>G 5_prime_UTR_variant Exon 1 of 9 1 ENSP00000401560.1 E9PDG3
WDR81ENST00000437219.6 linkc.51C>G p.Ser17Arg missense_variant Exon 1 of 10 2 ENSP00000391074.2 Q562E7-5
WDR81ENST00000455636.5 linkc.51C>G p.Ser17Arg missense_variant Exon 1 of 4 3 ENSP00000395226.1 C9JCF9

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152278
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000639
AC:
1
AN:
156536
Hom.:
0
AF XY:
0.0000121
AC XY:
1
AN XY:
82972
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:
0.00
Gnomad NFE exome
AF:
0.0000165
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000286
AC:
4
AN:
1399314
Hom.:
0
Cov.:
30
AF XY:
0.00000290
AC XY:
2
AN XY:
690150
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:
0.00
Gnomad4 FIN exome
AF:
0.0000406
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152278
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000302
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
15
DANN
Benign
0.90
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.74
FATHMM_MKL
Uncertain
0.82
D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.093
T
MVP
0.12
ClinPred
0.19
T
GERP RS
-1.1

Splicing

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: rs201917309; hg19: chr17-1619920; API