ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.7817T>A (p.Leu2606Ter) (rs749523755)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415153 SCV000492848 pathogenic Global developmental delay; Jaundice 2013-11-28 criteria provided, single submitter clinical testing
GeneDx RCV000255254 SCV000322599 pathogenic not provided 2017-10-05 criteria provided, single submitter clinical testing The L2606X pathogenic variant in the C5orf42 gene has been observed in an individual with Joubert syndrome and reported to be compound heterozygous with the c.1819delT frameshift variant; however, parental testing to confirm that the variants were in trans was not provided (Bachmann-Gagescu et al., 2015). Additionally, the L2606X variant has been observed with the A1200V variant in an individual with Oral-facial-digital syndrome type VI (OFDVI) phenotype; however, parental testing was not provided (Romani et al., 2015). The L2606X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000646703 SCV000768482 pathogenic Orofaciodigital syndrome 6; Joubert syndrome 17 2018-01-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu2606*) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs749523755, ExAC 0.005%). This variant has been reported as compound heterozygous with a second, rare C5orf42 variant in several individuals affected with Joubert syndrome (PMID: 25407461, 26092869) and an individual affected with oral-facial-digital syndrome, type VI (PMID: 25407461). ClinVar contains an entry for this variant (Variation ID: 217575). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic.
UW Hindbrain Malformation Research Program,University of Washington RCV000201773 SCV000256308 pathogenic Joubert syndrome 17 2015-02-23 criteria provided, single submitter research

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