Variant 4-176111695-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_181265.4(WDR17):c.115A>G(p.Ile39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

WDR17
NM_181265.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.743

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13050914).

BP6

Variant 4-176111695-A-G is Benign according to our data. Variant chr4-176111695-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2251859.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR17	NM_181265.4 linkuse as main transcript	c.115A>G	p.Ile39Val	missense_variant	2/29	ENST00000508596.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR17	ENST00000508596.6 linkuse as main transcript	c.115A>G	p.Ile39Val	missense_variant	2/29	1	NM_181265.4	P1	Q8IZU2-2
WDR17	ENST00000280190.8 linkuse as main transcript	c.187A>G	p.Ile63Val	missense_variant	3/31	1			Q8IZU2-1
WDR17	ENST00000507824.6 linkuse as main transcript	c.187A>G	p.Ile63Val	missense_variant	2/30	5
WDR17	ENST00000513261.1 linkuse as main transcript	c.187A>G	p.Ile63Val	missense_variant, NMD_transcript_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000419

AC:

AN:

238598

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426530

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.1

DANN

Benign

0.84

DEOGEN2

Benign

0.0097

.;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.71

D;D;D;D

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.66

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0020

.;B;B

Vest4

0.098

MutPred

0.38

.;Loss of catalytic residue at I63 (P = 0.2822);Loss of catalytic residue at I63 (P = 0.2822);

MVP

0.39

MPC

0.084

ClinPred

0.064

GERP RS

0.22

Varity_R

0.038

gMVP

0.11

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