ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.6012-2A>G

gnomAD frequency: 0.00001  dbSNP: rs555755221
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198220 SCV001369090 pathogenic Joubert syndrome 5 2019-07-09 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PM3,PP4.
Invitae RCV001211579 SCV001383124 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-21 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 43 of the CEP290 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with CEP290-related conditions (PMID: 24265693, 24850569). 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: 931558). 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 RCV003469314 SCV004216573 pathogenic Bardet-Biedl syndrome 14 2023-08-02 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828613 SCV002091855 pathogenic Leber congenital amaurosis 2020-02-13 no assertion criteria provided clinical testing

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