rs17617459

Positions:

chr2-63433768-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015910.7(WDPCP):c.802G>A(p.Gly268Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,612,906 control chromosomes in the GnomAD database, including 3,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 233 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2797 hom. )

Consequence

WDPCP
NM_015910.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.648

Variant links:

Genes affected

WDPCP (HGNC:28027): (WD repeat containing planar cell polarity effector) This gene encodes a cytoplasmic WD40 repeat protein. A similar gene in frogs encodes a planar cell polarity protein that plays a critical role in collective cell movement and ciliogenesis by mediating septin localization. Mutations in this gene are associated with Bardet-Biedl syndrome 15 and may also play a role in Meckel-Gruber syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

WDPCP links:

WDPCP (HGNC:):

WDPCP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019892156).

BP6

Variant 2-63433768-C-T is Benign according to our data. Variant chr2-63433768-C-T is described in ClinVar as [Benign]. Clinvar id is 260683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-63433768-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	NM_015910.7 linkuse as main transcript	c.802G>A	p.Gly268Ser	missense_variant	9/18	ENST00000272321.12	NP_056994.3	O95876-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12 linkuse as main transcript	c.802G>A	p.Gly268Ser	missense_variant	9/18	1	NM_015910.7	ENSP00000272321.7		O95876-1

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6565

AN:

151910

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0461

AC:

11470

AN:

248750

Hom.:

416

AF XY:

0.0462

AC XY:

6237

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.00943

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.0641

Gnomad OTH exome

AF:

0.0422

GnomAD4 exome

AF:

0.0565

AC:

82473

AN:

1460878

Hom.:

2797

Cov.:

AF XY:

0.0555

AC XY:

40351

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.0633

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0432

AC:

6564

AN:

152028

Hom.:

233

Cov.:

AF XY:

0.0439

AC XY:

3261

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0523

Hom.:

558

Bravo

AF:

0.0352

TwinsUK

AF:

0.0806

AC:

299

ALSPAC

AF:

0.0688

AC:

265

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.0598

AC:

490

ExAC

AF:

0.0474

AC:

5723

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Bardet-Biedl syndrome 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0012

T;.;.;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.71

T;.;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

N;.;.;.;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.10

N;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.49

T;T;T;T;T

Sift4G

Benign

0.64

T;T;T;T;T

Polyphen

0.010

B;B;B;B;B

Vest4

0.065

MPC

0.15

ClinPred

0.0023

GERP RS

4.6

Varity_R

0.061

gMVP

0.33

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