chr2-63259294-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_015910.7(WDPCP):c.1915+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,600,990 control chromosomes in the GnomAD database, including 249,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33809 hom., cov: 32)

Exomes 𝑓: 0.53 ( 215679 hom. )

Consequence

WDPCP
NM_015910.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.434

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 15
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
heart defect - tongue hamartoma - polysyndactyly syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

WDPCP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 2-63259294-C-T is Benign according to our data. Variant chr2-63259294-C-T is described in ClinVar as Benign. ClinVar VariationId is 95744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7 link	c.1915+13G>A		intron_variant	Intron 14 of 17	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.1915+13G>A		intron_variant	Intron 14 of 17	1	NM_015910.7	ENSP00000272321.7		O95876-1

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97256

AN:

151910

Hom.:

33761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.634

GnomAD2 exomes

AF:

0.604

AC:

149498

AN:

247674

AF XY:

0.599

show subpopulations

Gnomad AFR exome

AF:

0.903

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.854

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.501

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.534

AC:

773420

AN:

1448962

Hom.:

215679

Cov.:

AF XY:

0.538

AC XY:

388183

AN XY:

721810

show subpopulations

African (AFR)

AF:

0.907

AC:

30154

AN:

33228

American (AMR)

AF:

0.664

AC:

29660

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

17672

AN:

26014

East Asian (EAS)

AF:

0.853

AC:

33678

AN:

39478

South Asian (SAS)

AF:

0.721

AC:

61987

AN:

86004

European-Finnish (FIN)

AF:

0.420

AC:

21851

AN:

52000

Middle Eastern (MID)

AF:

0.672

AC:

3846

AN:

5726

European-Non Finnish (NFE)

AF:

0.490

AC:

540027

AN:

1101888

Other (OTH)

AF:

0.576

AC:

34545

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

15206

30412

45617

60823

76029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16074

32148

48222

64296

80370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.640

AC:

97362

AN:

152028

Hom.:

33809

Cov.:

AF XY:

0.639

AC XY:

47469

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.891

AC:

37018

AN:

41540

American (AMR)

AF:

0.647

AC:

9874

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2414

AN:

3472

East Asian (EAS)

AF:

0.849

AC:

4404

AN:

5186

South Asian (SAS)

AF:

0.722

AC:

3472

AN:

4812

European-Finnish (FIN)

AF:

0.409

AC:

4295

AN:

10514

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33805

AN:

67940

Other (OTH)

AF:

0.639

AC:

1344

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.566

Hom.:

9413

Bravo

AF:

0.667

Asia WGS

AF:

0.799

AC:

2775

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 06, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 1

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 2015

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 15

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

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

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 29, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Heart defect - tongue hamartoma - polysyndactyly syndrome

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over