rs267606693

chr2-63487491-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015910.7(WDPCP):c.164G>A(p.Arg55Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WDPCP NM_015910.7 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107883215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDPCP	NM_015910.7	c.164G>A	p.Arg55Lys	missense_variant	3/18	ENST00000272321.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDPCP	ENST00000272321.12	c.164G>A	p.Arg55Lys	missense_variant	3/18	1	NM_015910.7	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 247876 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134632

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439844 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 717674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Meckel syndrome, type 6, 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	0.096
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	18
Dann	Benign	0.91
DEOGEN2	Benign	0.0021	T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	0.87	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.10	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.29	T;T;.
Polyphen		0.022	B;B;.
Vest4		0.70
MutPred		0.40		Gain of ubiquitination at R55 (P = 0.0104);Gain of ubiquitination at R55 (P = 0.0104);Gain of ubiquitination at R55 (P = 0.0104);
MVP		0.76
MPC		0.15
ClinPred		0.20	T
GERP RS		4.6
Varity_R		0.091
gMVP		0.34

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: rs267606693; hg19: chr2-63714625;