Variant chr7-5225860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015610.4(WIPI2):c.778G>A(p.Gly260Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0021 in 1,613,680 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0043 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 55 hom. )

Consequence

WIPI2
NM_015610.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

WIPI2 (HGNC:32225): (WD repeat domain, phosphoinositide interacting 2) WD40 repeat proteins are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins, such as WIPI2, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids (Proikas-Cezanne et al., 2004 [PubMed 15602573]).[supplied by OMIM, Mar 2008]

WIPI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030396879).

BP6

Variant 7-5225860-G-A is Benign according to our data. Variant chr7-5225860-G-A is described in ClinVar as [Benign]. Clinvar id is 3033775.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIPI2	NM_015610.4 linkuse as main transcript	c.778G>A	p.Gly260Ser	missense_variant	9/13	ENST00000288828.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIPI2	ENST00000288828.9 linkuse as main transcript	c.778G>A	p.Gly260Ser	missense_variant	9/13	1	NM_015610.4		Q9Y4P8-1

Frequencies

GnomAD3 genomes

AF:

0.00427

AC:

649

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00470

AC:

1176

AN:

250204

Hom.:

AF XY:

0.00464

AC XY:

628

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.0464

Gnomad NFE exome

AF:

0.000928

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00187

AC:

2735

AN:

1461394

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1366

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00335

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.0398

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00426

AC:

648

AN:

152286

Hom.:

Cov.:

AF XY:

0.00665

AC XY:

495

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0499

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000509

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00380

AC:

462

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

WIPI2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 14, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.037

T;.;.;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D;D;D;D

MetaRNN

Benign

0.0030

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;.;N;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

2.3

N;N;N;N;N

REVEL

Benign

0.095

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.37

MVP

0.44

MPC

0.85

ClinPred

0.0060

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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