Variant 4-176125304-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181265.4(WDR17):c.739G>A(p.Val247Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00138 in 1,614,088 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

WDR17
NM_181265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

WDR17 (HGNC:16661): (WD repeat domain 17) This gene encodes a WD repeat-containing protein. It is abundantly expressed in retina and testis, and is thought to be a candidate gene for retinal disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2009]

WDR17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009039253).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR17	NM_181265.4 linkuse as main transcript	c.739G>A	p.Val247Ile	missense_variant	5/29	ENST00000508596.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR17	ENST00000508596.6 linkuse as main transcript	c.739G>A	p.Val247Ile	missense_variant	5/29	1	NM_181265.4	P1	Q8IZU2-2
WDR17	ENST00000280190.8 linkuse as main transcript	c.811G>A	p.Val271Ile	missense_variant	6/31	1			Q8IZU2-1
WDR17	ENST00000507824.6 linkuse as main transcript	c.760G>A	p.Val254Ile	missense_variant	5/30	5
WDR17	ENST00000505894.2 linkuse as main transcript	c.231+5207G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000720

AC:

181

AN:

251344

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00142

AC:

2077

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

982

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152228

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ExAC

AF:

0.000601

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00190

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.811G>A (p.V271I) alteration is located in exon 6 (coding exon 5) of the WDR17 gene. This alteration results from a G to A substitution at nucleotide position 811, causing the valine (V) at amino acid position 271 to be replaced by an isoleucine (I). 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

Benign

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0092

.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.4

.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.24

MVP

0.66

MPC

0.083

ClinPred

0.84

GERP RS

3.5

Varity_R

0.053

gMVP

0.22

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.

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