ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.493del (p.Ile165fs) (rs606231259)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193986 SCV000246835 pathogenic Joubert syndrome 17 2015-06-12 criteria provided, single submitter clinical testing
UW Hindbrain Malformation Research Program,University of Washington RCV000193986 SCV000256293 pathogenic Joubert syndrome 17 2015-02-23 criteria provided, single submitter research
Institute of Medical Genetics,University of Zurich RCV000193986 SCV000579463 pathogenic Joubert syndrome 17 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000521986 SCV000618307 pathogenic not provided 2020-08-26 criteria provided, single submitter clinical testing Frameshift 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; This variant is associated with the following publications: (PMID: 25407461, 24178751, 25920555, 29321670, 28289185, 26092869, 23523602)
Invitae RCV000646709 SCV000768488 pathogenic Orofaciodigital syndrome type 6; Joubert syndrome 17 2017-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile165Tyrfs*17) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with Joubert syndrome (PMID: 25920555, 26092869, 28289185), as well as in individuals affected with Oral-Facial-Digital syndrome (PMID: 24178751). ClinVar contains an entry for this variant (Variation ID: 157513). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics, Johns Hopkins University RCV000193986 SCV001441549 pathogenic Joubert syndrome 17 2020-10-27 criteria provided, single submitter clinical testing This CPLANE1 variant (rs968241708) is rare (<0.1%) in a large population dataset (25/188678 total alleles; 0.013%; no homozygotes) and has an entry in ClinVar. This variant has been reported previously in a compound heterozygous state in multiple unrelated individuals affected with JS or Oral-Facial-Digital syndrome (OFD). This frameshift variant results in a premature stop codon in exon 5 of 52 likely leading to nonsense-mediated decay and lack of protein production. We consider c.493delA to be pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000193986 SCV001445910 pathogenic Joubert syndrome 17 2019-08-07 criteria provided, single submitter clinical testing This frameshifting variant in exon 5 of 52 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a compound heterozygous change in patients with Joubert syndrome (PMID: 25920555, 26092869, 28289185, 25407461, 29321670), as well as in individuals affected with Oral-Facial-Digital syndrome (PMID: 24178751). ClinVar contains an entry for this variant (Variation ID: 157513). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.013% (25/188678) and thus is presumed to be rare. Based on the available evidence, the c.493del (p.Ile165TyrfsTer17) variant is classified as Pathogenic.
Invitae RCV000521986 SCV001592113 pathogenic not provided 2017-08-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile165Tyrfs*17) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with Joubert syndrome (PMID: 25920555, 26092869, 28289185), as well as in individuals affected with Oral-Facial-Digital syndrome (PMID: 24178751). ClinVar contains an entry for this variant (Variation ID: 157513). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic. 1
OMIM RCV000144858 SCV000191878 pathogenic Orofaciodigital syndrome type 6 2014-03-01 no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000193986 SCV001430059 pathogenic Joubert syndrome 17 2020-01-16 no assertion criteria provided clinical testing

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