chr2-63174685-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015910.7(WDPCP):c.2063A>G(p.Asn688Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,868 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 8 hom., cov: 32)

Exomes 𝑓: 0.013 ( 151 hom. )

Consequence

WDPCP
NM_015910.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.142

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:

ENSG00000286480 (HGNC:):

ENSG00000286480 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037649274).

BP6

Variant 2-63174685-T-C is Benign according to our data. Variant chr2-63174685-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 220870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-63174685-T-C is described in Lovd as [Benign]. Variant chr2-63174685-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00894 (1362/152298) while in subpopulation NFE AF= 0.0151 (1029/68018). AF 95% confidence interval is 0.0144. There are 8 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7 link	c.2063A>G	p.Asn688Ser	missense_variant	Exon 15 of 18	ENST00000272321.12	NP_056994.3	O95876-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12 link	c.2063A>G	p.Asn688Ser	missense_variant	Exon 15 of 18	1	NM_015910.7	ENSP00000272321.7		O95876-1

Frequencies

GnomAD3 genomes

AF:

0.00894

AC:

1361

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00942

AC:

2348

AN:

249322

Hom.:

AF XY:

0.0100

AC XY:

1359

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.00417

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0130

AC:

18952

AN:

1461570

Hom.:

151

Cov.:

AF XY:

0.0130

AC XY:

9475

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00720

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.00479

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.00976

GnomAD4 genome

AF:

0.00894

AC:

1362

AN:

152298

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

624

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00871

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00829

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00325

AC:

ESP6500EA

AF:

0.0169

AC:

138

ExAC

AF:

0.00991

AC:

1197

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0136

EpiControl

AF:

0.0130

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WDPCP: BP4, BS1, BS2 -

Aug 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 1

Benign:2

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 15

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Bardet-Biedl syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.8

DANN

Benign

0.85

DEOGEN2

Benign

0.00074

T;.;.;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.75

T;.;T;T

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.080

N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.058

T;T;T;T

Sift4G

Benign

0.37

T;T;T;T

Polyphen

0.0010

B;.;.;B

Vest4

0.072

MVP

0.59

MPC

0.088

ClinPred

0.0010

GERP RS

2.8

Varity_R

0.049

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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