ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1987A>T (p.Lys663Ter)

dbSNP: rs2038919221
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001383423 SCV001582564 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys663*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of CEP290-related conditions (PMID: 23188109, 29053603). ClinVar contains an entry for this variant (Variation ID: 1071061). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003469695 SCV004214875 pathogenic Bardet-Biedl syndrome 14 2024-02-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005057356 SCV005726902 pathogenic Meckel syndrome, type 4 2024-11-08 criteria provided, single submitter clinical testing Variant summary: CEP290 c.1987A>T (p.Lys663X) 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. The variant was absent in 156574 control chromosomes (gnomAD). c.1987A>T has been reported in the literature in individuals affected with CEP290-Related Disorders (e.g. Di Iorio_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29053603). ClinVar contains an entry for this variant (Variation ID: 1071061). Based on the evidence outlined above, the variant was classified as pathogenic.

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