rs727503781
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015910.7(WDPCP):c.552_553del(p.Cys185PhefsTer12) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000688 in 1,599,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
WDPCP
NM_015910.7 frameshift
NM_015910.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.11
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-63437500-CAT-C is Pathogenic according to our data. Variant chr2-63437500-CAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 162668.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDPCP | NM_015910.7 | c.552_553del | p.Cys185PhefsTer12 | frameshift_variant | 8/18 | ENST00000272321.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDPCP | ENST00000272321.12 | c.552_553del | p.Cys185PhefsTer12 | frameshift_variant | 8/18 | 1 | NM_015910.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151816Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000417 AC: 1AN: 239650Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129838
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GnomAD4 exome AF: 0.00000622 AC: 9AN: 1447686Hom.: 0 AF XY: 0.00000973 AC XY: 7AN XY: 719644
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74260
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Heart defect - tongue hamartoma - polysyndactyly syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2015 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at