rs147416429
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001384732.1(CPLANE1):c.8140C>T(p.Arg2714Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000247 in 1,458,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
CPLANE1
NM_001384732.1 stop_gained
NM_001384732.1 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 5-37153973-G-A is Pathogenic according to our data. Variant chr5-37153973-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 217566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37153973-G-A is described in Lovd as [Pathogenic]. Variant chr5-37153973-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPLANE1 | NM_001384732.1 | c.8140C>T | p.Arg2714Ter | stop_gained | 42/53 | ENST00000651892.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPLANE1 | ENST00000651892.2 | c.8140C>T | p.Arg2714Ter | stop_gained | 42/53 | NM_001384732.1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249488Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134794
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GnomAD4 exome AF: 0.0000247 AC: 36AN: 1458048Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 724700
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4Uncertain:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Joubert syndrome 17 Pathogenic:2Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Neurology Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Dr.Nikuei Genetic Center | - | - - |
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217566). This variant is also known as C5ORF42 p.R2660X. This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 22693042, 26092869, 33176815). This variant is present in population databases (rs147416429, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg2660*) in the CPLANE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CPLANE1 are known to be pathogenic (PMID: 24178751, 26092869). - |
Orofaciodigital syndrome type 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 18, 2019 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
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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