rs200322968

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PP3_StrongPP5

The NM_015910.7(WDPCP):c.160G>A(p.Asp54Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000234 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

WDPCP
NM_015910.7 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:4U:5

Conservation

PhyloP100: 5.69

Publications

7 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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: Uncertain_significance. The variant received 5 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

PP5

Variant 2-63492856-C-T is Pathogenic according to our data. Variant chr2-63492856-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 162669.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015910.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDPCP	NM_015910.7	MANE Select	c.160G>A	p.Asp54Asn	missense splice_region	Exon 2 of 18	NP_056994.3	O95876-1
WDPCP	NM_001354044.2		c.88G>A	p.Asp30Asn	missense splice_region	Exon 3 of 19	NP_001340973.1
WDPCP	NM_001354045.2		c.160G>A	p.Asp54Asn	missense splice_region	Exon 2 of 13	NP_001340974.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDPCP	ENST00000272321.12	TSL:1 MANE Select	c.160G>A	p.Asp54Asn	missense splice_region	Exon 2 of 18	ENSP00000272321.7	O95876-1
WDPCP	ENST00000409562.7	TSL:1	c.160G>A	p.Asp54Asn	missense splice_region	Exon 2 of 14	ENSP00000387222.3	O95876-2
WDPCP	ENST00000409835.5	TSL:1	n.407G>A		splice_region non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes

AF:

0.0000988

AC:

AN:

151824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000133

AC:

AN:

248530

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461026

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

726806

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33448

American (AMR)

AF:

0.000179

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000300

AC:

334

AN:

1111508

Other (OTH)

AF:

0.000282

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000988

AC:

AN:

151824

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41290

American (AMR)

AF:

0.000131

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000197

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Heart defect - tongue hamartoma - polysyndactyly syndrome (4)

Heart defect - tongue hamartoma - polysyndactyly syndrome;C3150127:Bardet-Biedl syndrome 15 (2)

Bardet-Biedl syndrome (1)

Orofaciodigital syndrome (1)

WDPCP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.59

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.1

PhyloP100

5.7

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

REVEL

Pathogenic

0.74

Sift

Benign

0.033

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.65

MVP

0.90

MPC

0.51

ClinPred

0.45

GERP RS

5.4

Varity_R

0.30

gMVP

0.45

Mutation Taster

=4/96

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

1.0

SpliceAI score (max)

0.79

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.79

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over