Variant 17-1730810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000446363(WDR81):c.-253C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 1,612,388 control chromosomes in the GnomAD database, including 8,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 805 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8059 hom. )

Consequence

WDR81
ENST00000446363 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.79

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]

WDR81 links:

WDR81 (HGNC:):

WDR81 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-1730810-C-T is Benign according to our data. Variant chr17-1730810-C-T is described in ClinVar as [Benign]. Clinvar id is 130738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR81	NM_001163809.2 linkuse as main transcript	c.3831C>T	p.Ala1277Ala	synonymous_variant	3/10	ENST00000409644.6	NP_001157281.1	Q562E7-1Q24JR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR81	ENST00000409644.6 linkuse as main transcript	c.3831C>T	p.Ala1277Ala	synonymous_variant	3/10	1	NM_001163809.2	ENSP00000386609.1		Q562E7-1

Frequencies

GnomAD3 genomes

AF:

0.0937

AC:

14258

AN:

152138

Hom.:

803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0676

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0687

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.119

AC:

29305

AN:

247274

Hom.:

2104

AF XY:

0.118

AC XY:

15828

AN XY:

134396

show subpopulations

Gnomad AFR exome

AF:

0.0655

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.0693

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.0999

AC:

145871

AN:

1460132

Hom.:

8059

Cov.:

AF XY:

0.101

AC XY:

73659

AN XY:

726392

show subpopulations

Gnomad4 AFR exome

AF:

0.0675

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0694

Gnomad4 NFE exome

AF:

0.0905

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0937

AC:

14259

AN:

152256

Hom.:

805

Cov.:

AF XY:

0.0976

AC XY:

7266

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0687

Gnomad4 NFE

AF:

0.0882

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0913

Hom.:

1013

Bravo

AF:

0.0990

Asia WGS

AF:

0.131

AC:

454

AN:

3478

EpiCase

AF:

0.0960

EpiControl

AF:

0.0958

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.16

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over