rs779680371
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001384732.1(CPLANE1):βc.510delβ(p.Leu171SerfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 31)
Exomes π: 0.000016 ( 0 hom. )
Consequence
CPLANE1
NM_001384732.1 frameshift
NM_001384732.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.368
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]
Genome browser will be placed here
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 5-37244434-GA-G is Pathogenic according to our data. Variant chr5-37244434-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 217578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37244434-GA-G is described in Lovd as [Pathogenic]. Variant chr5-37244434-GA-G is described in Lovd as [Pathogenic]. Variant chr5-37244434-GA-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPLANE1 | NM_001384732.1 | c.510del | p.Leu171SerfsTer11 | frameshift_variant | 5/53 | ENST00000651892.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPLANE1 | ENST00000651892.2 | c.510del | p.Leu171SerfsTer11 | frameshift_variant | 5/53 | NM_001384732.1 | A2 | ||
CPLANE1 | ENST00000508244.5 | c.510del | p.Leu171SerfsTer11 | frameshift_variant | 4/51 | 5 | P2 | ||
CPLANE1 | ENST00000425232.7 | c.293del | p.Leu99SerfsTer11 | frameshift_variant, NMD_transcript_variant | 2/30 | 5 | |||
CPLANE1 | ENST00000675547.1 | n.640+1044del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151848Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
2
AN:
151848
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000164 AC: 23AN: 1399360Hom.: 0 Cov.: 31 AF XY: 0.0000174 AC XY: 12AN XY: 690170
GnomAD4 exome
AF:
AC:
23
AN:
1399360
Hom.:
Cov.:
31
AF XY:
AC XY:
12
AN XY:
690170
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151848Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74138
GnomAD4 genome
?
AF:
AC:
2
AN:
151848
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74138
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 03, 2021 | - - |
Joubert syndrome 17 Pathogenic:1
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 | Nov 27, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CPLANE1 are known to be pathogenic (PMID: 22425360, 24178751). This variant has been observed in an individual within a cohort of individuals who have clinical findings of Joubert syndrome or have a sibling with Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217578). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu171Serfs*11) in the CPLANE1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at