Variant 7-5216554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015610.4(WIPI2):c.382-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,613,908 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 24 hom. )

Consequence

WIPI2
NM_015610.4 intron

Scores

Splicing: ADA: 0.00003477

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0430

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-5216554-C-T is Benign according to our data. Variant chr7-5216554-C-T is described in ClinVar as [Benign]. Clinvar id is 710689.Status of the report is criteria_provided_single_submitter, 1 stars.

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.382-9C>T		intron_variant		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.382-9C>T		intron_variant		1	NM_015610.4	ENSP00000288828.4		Q9Y4P8-1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00389

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00385

AC:

966

AN:

251220

Hom.:

AF XY:

0.00379

AC XY:

514

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.00402

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00354

AC:

5168

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

2501

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0218

Gnomad4 NFE exome

AF:

0.00340

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.00344

AC:

524

AN:

152318

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

316

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0220

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00343

Hom.:

Bravo

AF:

0.00165

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00235

EpiControl

AF:

0.00225

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

Jan 09, 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

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.3

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.060

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