2-63404150-C-G

Position:

chr2-63404150-C-G

Variant summary

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

The NM_015910.7(WDPCP):c.1333G>C(p.Ala445Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,614,098 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 59 hom. )

Consequence

WDPCP
NM_015910.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.50

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:

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=0.008161902).

BP6

Variant 2-63404150-C-G is Benign according to our data. Variant chr2-63404150-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 193723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-63404150-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00551 (839/152288) while in subpopulation NFE AF= 0.00972 (661/68022). AF 95% confidence interval is 0.0091. There are 2 homozygotes in gnomad4. There are 371 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	NM_015910.7 linkuse as main transcript	c.1333G>C	p.Ala445Pro	missense_variant	10/18	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12 linkuse as main transcript	c.1333G>C	p.Ala445Pro	missense_variant	10/18	1	NM_015910.7	ENSP00000272321	P1	O95876-1

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

840

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00973

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00565

AC:

1407

AN:

248940

Hom.:

AF XY:

0.00578

AC XY:

780

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00339

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00779

AC:

11391

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

5472

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00350

Gnomad4 NFE exome

AF:

0.00955

Gnomad4 OTH exome

AF:

0.00619

GnomAD4 genome

AF:

0.00551

AC:

839

AN:

152288

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

371

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00972

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00753

Hom.:

Bravo

AF:

0.00499

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00157

AC:

ESP6500EA

AF:

0.00980

AC:

ExAC

AF:

0.00660

AC:

797

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00786

EpiControl

AF:

0.00812

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	WDPCP: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 12, 2015	- -

Bardet-Biedl syndrome 15

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 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

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

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0042

T;.;.;.;.

Eigen

Benign

-0.0044

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;.;D;D;D

MetaRNN

Benign

0.0082

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.7

L;.;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.52

N;N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.076

B;B;B;B;D

Vest4

0.48

MVP

0.55

MPC

0.61

ClinPred

0.012

GERP RS

4.7

Varity_R

0.19

gMVP

0.41

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