ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5776C>T (p.Arg1926Ter) (rs561598805)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group, Broad Institute RCV000785894 SCV000924470 likely pathogenic Joubert syndrome 5 2018-06-15 criteria provided, single submitter research The homozygous p.Arg1926Ter variant was identified by our study in one individual with Joubert syndrome. This variant has been identified in the literature in one individual with Joubert syndrome (Stone E., PMID:17964524). This variant has been identified in <0.01% (1/16406) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs561598805). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the CEP290 gene is an established disease mechanism in autosomal recessive Joubert syndrome, and this is a loss of function variant. In summary, although additional studies are required to fully establish its pathogenicity, this variant is likely pathogenic.
Invitae RCV001207057 SCV001378396 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2020-05-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1926*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs561598805, ExAC 0.01%). This variant has been observed in an individual affected with Leber congenital amaurosis (PMID: 17964524). 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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