Variant chr7-5227327-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_015610.4(WIPI2):c.996C>T(p.Asn332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,613,604 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 160 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 131 hom. )

Consequence

WIPI2
NM_015610.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.17

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 7-5227327-C-T is Benign according to our data. Variant chr7-5227327-C-T is described in ClinVar as [Benign]. Clinvar id is 778276.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIPI2	NM_015610.4 linkuse as main transcript	c.996C>T	p.Asn332=	synonymous_variant	10/13	ENST00000288828.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIPI2	ENST00000288828.9 linkuse as main transcript	c.996C>T	p.Asn332=	synonymous_variant	10/13	1	NM_015610.4		Q9Y4P8-1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3986

AN:

152248

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00679

AC:

1700

AN:

250186

Hom.:

AF XY:

0.00501

AC XY:

678

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.0889

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00281

AC:

4105

AN:

1461238

Hom.:

131

Cov.:

AF XY:

0.00253

AC XY:

1838

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.0902

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.00624

GnomAD4 genome

AF:

0.0262

AC:

3999

AN:

152366

Hom.:

160

Cov.:

AF XY:

0.0255

AC XY:

1899

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0902

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00751

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

WIPI2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 29, 2019

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

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.2

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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