ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1645C>T (p.Arg549Ter)

gnomAD frequency: 0.00001  dbSNP: rs760415289
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810414 SCV000950612 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-12-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg549*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is present in population databases (rs760415289, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with CEP290-related conditions (PMID: 17409309, 22355252, 27434533). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 654447). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091339 SCV001247307 pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002487758 SCV002800589 pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-05-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV003467439 SCV004216521 pathogenic Bardet-Biedl syndrome 14 2024-03-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274127 SCV001457924 pathogenic Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001091339 SCV001952405 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001091339 SCV001974887 pathogenic not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733051 SCV005360907 pathogenic CEP290-related disorder 2024-07-09 no assertion criteria provided clinical testing The CEP290 c.1645C>T variant is predicted to result in premature protein termination (p.Arg549*). This variant along with a second CEP290 variant has been reported in one patient with Joubert syndrome (Stone et al. 2017. PubMed ID: 28559085 Table S1 in supplement 3). This variant was also found in another patient with autosomal recessive Leber congenital amaurosis (Yzer et al. 2012. PubMed ID: 22355252). This variant is reported in 0.0072% of alleles in individuals of South Asian descent in gnomAD. Nonsense variants in CEP290 are expected to be pathogenic. This variant is interpreted as pathogenic.

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