dbSNP rs201412509: WDPCP:p.Val480Phe (chr2-63382092-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015910.7(WDPCP):c.1438G>T(p.Val480Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V480I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDPCP
NM_015910.7 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.350

Publications

3 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDPCP	NM_015910.7 link	c.1438G>T	p.Val480Phe	missense_variant, splice_region_variant	Exon 11 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.1438G>T	p.Val480Phe	missense_variant, splice_region_variant	Exon 11 of 18	1	NM_015910.7	ENSP00000272321.7		O95876-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246666

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460030

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111236

Other (OTH)

AF:

0.00

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;.;D;D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.64

D;D;D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;.;.;.;L

PhyloP100

0.35

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.8

D;D;D;D;N

REVEL

Benign

0.14

Sift

Benign

0.048

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

0.92

P;.;.;P;P

Vest4

0.57

MutPred

0.25

Loss of sheet (P = 0.0357);.;.;.;Loss of sheet (P = 0.0357);

MVP

0.54

MPC

0.49

ClinPred

0.89

GERP RS

0.32

Varity_R

0.19

gMVP

0.35

Mutation Taster

=87/13

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over