Variant rs189817127 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The ENST00000272321.12(WDPCP):c.1263A>C(p.Leu421Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

WDPCP
ENST00000272321.12 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.923

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 -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011816651).

BP6

Variant 2-63404220-T-G is Benign according to our data. Variant chr2-63404220-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 462949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00131 (200/152270) while in subpopulation AFR AF= 0.0045 (187/41554). AF 95% confidence interval is 0.00397. There are 1 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	NM_015910.7 linkuse as main transcript	c.1263A>C	p.Leu421Phe	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.1263A>C	p.Leu421Phe	missense_variant	10/18	1	NM_015910.7	ENSP00000272321	P1	O95876-1

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

199

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

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:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000350

AC:

AN:

248426

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.00446

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1461516

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00400

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152270

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00450

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000358

Hom.:

Bravo

AF:

0.00140

ESP6500AA

AF:

0.00260

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000372

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0037

T;.;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.039

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

D;.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.;L

MutationTaster

Benign

0.91

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.41

B;B;B;B;P

Vest4

0.052

MutPred

0.19

Loss of stability (P = 0.0821);.;.;.;Loss of stability (P = 0.0821);

MVP

0.51

MPC

0.42

ClinPred

0.0061

GERP RS

3.0

Varity_R

0.058

gMVP

0.13

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

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