ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.7198C>T (p.Gln2400Ter)

dbSNP: rs1478582091
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001825112 SCV002074351 likely pathogenic CEP290-related disorder 2022-01-19 criteria provided, single submitter clinical testing Variant summary: CEP290 c.7198C>T (p.Gln2400X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in HGMD in association with Leber congenital amaurosis, Nephronophthisis-related ciliopathy, and Joubert syndrome. The variant was absent in 231354 control chromosomes. To our knowledge, no occurrence of c.7198C>T in individuals affected with CEP290-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002503334 SCV002810988 likely pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-06 criteria provided, single submitter clinical testing
Invitae RCV002545200 SCV003311732 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2400*) in the CEP290 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acid(s) of the CEP290 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 1339724). This variant disrupts a region of the CEP290 protein in which other variant(s) (p.Leu2448Thrfs*8) have been determined to be pathogenic (PMID: 16682973, 16909394, 29588463). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003470936 SCV004214876 likely pathogenic Bardet-Biedl syndrome 14 2023-10-05 criteria provided, single submitter clinical testing

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