ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.297+1G>T

gnomAD frequency: 0.00001  dbSNP: rs878853360
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001223284 SCV001395424 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-02-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 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 not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with CEP290-related conditions (PMID: 22699515, 25097241, 28973549). ClinVar contains an entry for this variant (Variation ID: 236464). 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.
Revvity Omics, Revvity RCV001782716 SCV002017018 pathogenic not provided 2020-12-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155133 SCV003844815 pathogenic Meckel syndrome, type 4 2023-02-15 criteria provided, single submitter clinical testing Variant summary: CEP290 c.297+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 144540 control chromosomes. c.297+1G>T has been reported in the literature in individuals affected with CEP290-related disorders. These data indicate that the variant may be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003469116 SCV004214858 pathogenic Bardet-Biedl syndrome 14 2024-01-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005003571 SCV005632057 likely pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-03-13 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV000225517 SCV000282570 uncertain significance Retinal dystrophy no assertion criteria provided clinical testing
Natera, Inc. RCV001833239 SCV002094942 pathogenic Leber congenital amaurosis 2021-10-13 no assertion criteria provided clinical testing

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