ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.7477C>T (p.Arg2493Ter) (rs139675596)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000024222 SCV000256296 pathogenic Joubert syndrome 17 2015-02-23 criteria provided, single submitter research
Invitae RCV000024222 SCV000652568 pathogenic Joubert syndrome 17 2017-06-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2493*) in the C5orf42 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs139675596, ExAC 0.01%). This variant has been reported to segregate with Joubert syndrome in a single family (PMID: 22425360, 23012439). It has also been reported in several additional individuals affected with Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 31223). Loss-of-function variants in C5orf42 are known to be pathogenic (PMID: 22425360). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763544 SCV000894357 pathogenic Orofaciodigital syndrome type 6; Joubert syndrome 17 2018-10-31 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000024222 SCV001164436 pathogenic Joubert syndrome 17 2018-12-03 criteria provided, single submitter research The homozygous p.Arg2493Ter variant in C5orf42 was identified by our study in one individual with Joubert syndrome. This variant has been identified in 0.005767% (14/242764) of chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs139675596). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The p.Arg2493Ter variant in C5orf42 has been reported as a causative variant in 3 mixed European and Native American families with Joubert syndrome and in the compound heterozygous state in one individual with a missense variant, which has been reported in trans with 3 other loss of function variants (PMID: 26092869, 22425360). Loss of function of the C5orf42 gene is an established disease mechanism for autosomal recessive Joubert syndrome, and this is a loss of function variant. In summary, the p.Arg2493Ter variant is pathogenic. ACMG/AMP Criteria applied: PM2, PP3, PM3_Supporting (Richards 2015).
OMIM RCV000024222 SCV000045513 pathogenic Joubert syndrome 17 2012-04-06 no assertion criteria provided literature only
GeneReviews RCV000024222 SCV000058555 pathologic Joubert syndrome 17 2012-03-29 no assertion criteria provided curation Converted during submission to Pathogenic.

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