rs749523755
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001384732.1(CPLANE1):c.7871T>A(p.Leu2624Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,394 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
Consequence
NM_001384732.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPLANE1 | NM_001384732.1 | c.7871T>A | p.Leu2624Ter | stop_gained | 40/53 | ENST00000651892.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPLANE1 | ENST00000651892.2 | c.7871T>A | p.Leu2624Ter | stop_gained | 40/53 | NM_001384732.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251054Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135726
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461438Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727054
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151956Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74202
ClinVar
Submissions by phenotype
not provided Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2021 | This sequence change creates a premature translational stop signal (p.Leu2606*) 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). This variant is present in population databases (rs749523755, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with Joubert syndrome and oral-facial-digital syndrome, type VI (PMID: 25407461, 26092869). ClinVar contains an entry for this variant (Variation ID: 217575). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in a patient with clinical features of oral-facial-digital type VI with a second CPLANE1(aka C5orf42) variant (Romani et al., 2015); This variant is associated with the following publications: (PMID: 26092869, 28497568, 25407461) - |
Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Orofaciodigital syndrome type 6;C3553264:Joubert syndrome 17 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 15, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 05, 2021 | - - |
Joubert syndrome 17 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Jaundice;C0557874:Global developmental delay Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Nov 28, 2013 | - - |
Orofaciodigital syndrome type 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Nov 26, 2018 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at