chr2-63437430-C-G

Position:

• chr2-63437430-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015910.7(WDPCP):​c.624G>C​(p.Leu208Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDPCP NM_015910.7 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.97

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2848223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDPCP	NM_015910.7	c.624G>C	p.Leu208Phe	missense_variant	8/18	ENST00000272321.12	NP_056994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDPCP	ENST00000272321.12	c.624G>C	p.Leu208Phe	missense_variant	8/18	1	NM_015910.7	ENSP00000272321.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-Biedl syndrome 12, modifier of Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 10, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;.;.;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T;.;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.2	M;.;.;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.019	D;D;D;D;D
Sift4G	Uncertain	0.046	D;D;D;D;T
Polyphen		0.80	P;P;P;P;D
Vest4		0.34
MutPred		0.25		Gain of sheet (P = 0.0827);.;.;.;Gain of sheet (P = 0.0827);
MVP		0.67
MPC		0.55
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.19

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

Other links and lift over

dbSNP: rs267606692; hg19: chr2-63664564;