Variant 7-5214587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_015610.4(WIPI2):c.264G>A(p.Val88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,614,246 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 30 hom., cov: 33)

Exomes 𝑓: 0.018 ( 297 hom. )

Consequence

WIPI2
NM_015610.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.15

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-5214587-G-A is Benign according to our data. Variant chr7-5214587-G-A is described in ClinVar as [Benign]. Clinvar id is 3057208.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0142 (2162/152358) while in subpopulation SAS AF= 0.0218 (105/4826). AF 95% confidence interval is 0.0184. There are 30 homozygotes in gnomad4. There are 1174 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIPI2	NM_015610.4 linkuse as main transcript	c.264G>A	p.Val88=	synonymous_variant	4/13	ENST00000288828.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIPI2	ENST00000288828.9 linkuse as main transcript	c.264G>A	p.Val88=	synonymous_variant	4/13	1	NM_015610.4		Q9Y4P8-1

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2163

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0177

AC:

4457

AN:

251494

Hom.:

AF XY:

0.0186

AC XY:

2529

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.0481

Gnomad NFE exome

AF:

0.0204

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0175

AC:

25593

AN:

1461888

Hom.:

297

Cov.:

AF XY:

0.0177

AC XY:

12877

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0222

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0142

AC:

2162

AN:

152358

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1174

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.00620

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.0471

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0172

Hom.:

Bravo

AF:

0.00981

Asia WGS

AF:

0.00837

AC:

AN:

3478

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

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

-0.46

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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