Variant 7-5225871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_015610.4(WIPI2):c.789C>T(p.Leu263Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,896 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

WIPI2
NM_015610.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.273

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:

WIPI2 (HGNC:):

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 (BayesDel_noAF=-0.28).

BP6

Variant 7-5225871-C-T is Benign according to our data. Variant chr7-5225871-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657267.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.273 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPI2	NM_015610.4 linkuse as main transcript	c.789C>T	p.Leu263Leu	synonymous_variant	9/13	ENST00000288828.9	NP_056425.1	Q9Y4P8-1A0A024R823

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPI2	ENST00000288828.9 linkuse as main transcript	c.789C>T	p.Leu263Leu	synonymous_variant	9/13	1	NM_015610.4	ENSP00000288828.4		Q9Y4P8-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

159

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00152

AC:

380

AN:

250646

Hom.:

AF XY:

0.00183

AC XY:

248

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00509

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00119

AC:

1741

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

988

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00536

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000810

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00104

AC:

159

AN:

152340

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00538

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.000952

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

Feb 01, 2024

WIPI2: BP4, BP7, BS2 -

WIPI2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2020

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.28

CADD

Benign

9.7

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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