ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4705-1G>T

gnomAD frequency: 0.00001  dbSNP: rs777464278
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479832 SCV000568656 likely pathogenic not provided 2019-12-05 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame deletion of colied coil region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28157192, 22334370)
Labcorp Genetics (formerly Invitae), Labcorp RCV001060437 SCV001225124 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 35 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). This variant is present in population databases (rs777464278, gnomAD 0.02%). Disruption of this splice site has been observed in individuals with retinitis pigmentosa (PMID: 22334370, 28157192). ClinVar contains an entry for this variant (Variation ID: 420091). 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 RCV001335139 SCV001528203 pathogenic Joubert syndrome 5 2018-01-09 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID 22334370]
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003324527 SCV004030368 pathogenic Leber congenital amaurosis 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
PreventionGenetics, part of Exact Sciences RCV004527588 SCV004107453 pathogenic CEP290-related disorder 2023-06-16 criteria provided, single submitter clinical testing The CEP290 c.4705-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in the compound heterozygous state with another protein truncating variant in at least three individuals with retinitis pigmentosa or other retinal dystrophies (Neveling et al. 2012. PubMed ID: 22334370; Bravo-Gil et al. 2017. PubMed ID: 28157192; Testa et al. 2021. PubMed ID: 34196655). This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88477732-C-A). Variants that disrupt the consensus splice acceptor site in CEP290 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV003470556 SCV004216595 pathogenic Bardet-Biedl syndrome 14 2024-03-26 criteria provided, single submitter clinical testing

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