Variant 17-1716626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000446363.5(WDR81):c.-397C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,551,704 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 6 hom. )

Consequence

WDR81
ENST00000446363.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

WDR81 links:

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

MIR22HG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00956881).

BP6

Variant 17-1716626-C-T is Benign according to our data. Variant chr17-1716626-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1716626-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00209 (319/152396) while in subpopulation NFE AF= 0.00357 (243/68034). AF 95% confidence interval is 0.0032. There are 0 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR81	NM_001163673.2 linkuse as main transcript	c.51C>T	p.Ser17=	synonymous_variant	1/10
WDR81	NM_152348.4 linkuse as main transcript	c.-131C>T		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR22HG	ENST00000577164.2 linkuse as main transcript	n.139-354G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

319

AN:

152278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00357

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00187

AC:

293

AN:

156536

Hom.:

AF XY:

0.00183

AC XY:

152

AN XY:

82972

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.000932

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000703

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00315

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.00334

AC:

4676

AN:

1399308

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

2190

AN XY:

690146

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00266

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00350

GnomAD4 genome

AF:

0.00209

AC:

319

AN:

152396

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74528

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00216

Gnomad4 NFE

AF:

0.00357

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00346

AC:

ExAC

AF:

0.00118

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

WDR81: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.030

FATHMM_MKL

Uncertain

0.80

MetaRNN

Benign

0.0096

MutationTaster

Benign

1.0

D;D;D

MVP

0.68

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.

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