ClinVar Miner

Submissions for variant NM_025114.3(CEP290):c.6277delG (p.Val2093Serfs) (rs771454167)

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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 RCV000201679 SCV000256367 pathogenic Joubert syndrome 5 2015-02-23 criteria provided, single submitter research
GeneDx RCV000487320 SCV000568655 pathogenic not provided 2017-01-03 criteria provided, single submitter clinical testing The c.6277delG variant in the CEP290 gene has been reported previously in association with Joubert syndrome (Brancati et al., 2007; Chaki et al., 2011). This variant causes a frameshift starting with codon Valine 2093, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Val2093SerfsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.6277delG variant was not observed in approximately 5900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.6277delG as a pathogenic variant.
Genetic Services Laboratory,University of Chicago RCV000501294 SCV000594071 pathogenic Bardet-Biedl syndrome 14 2015-08-07 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000201679 SCV001149703 pathogenic Joubert syndrome 5 2020-01-16 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV001002716 SCV001156392 pathogenic Senior-Loken syndrome 6 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV001224012 SCV001396185 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2019-06-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val2093Serfs*4) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs771454167, ExAC 0.02%). This variant has been observed in several individuals affected with CEP290-related conditions (PMID: 17564967, 21866095, 26092869). ClinVar contains an entry for this variant (Variation ID: 217621). Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115, 25377065, 28559085). For these reasons, this variant has been classified as Pathogenic.

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