Submissions for variant NM_025114.4(CEP290):c.2052+1_2052+2del

dbSNP: rs747835249

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000387808	SCV000334141	pathogenic	not provided	2016-06-05	criteria provided, single submitter	clinical testing
Invitae	RCV000692104	SCV000819912	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change affects a splice site in intron 20 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 (rs747835249, gnomAD 0.005%). Disruption of this splice site has been observed in individuals with Leber congenital amaurosis (LCA) (PMID: 23847139, 28510626, 28660274). ClinVar contains an entry for this variant (Variation ID: 236466). 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.
Blueprint Genetics	RCV000225427	SCV001240406	pathogenic	Retinal dystrophy	2019-07-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000387808	SCV001982098	pathogenic	not provided	2021-07-13	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32865313, 23847139, 31589614, 27535533)
Fulgent Genetics, Fulgent Genetics	RCV002503881	SCV002808947	pathogenic	Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	2021-09-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003469117	SCV004214867	pathogenic	Bardet-Biedl syndrome 14	2023-10-13	criteria provided, single submitter	clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225427	SCV000282572	likely pathogenic	Retinal dystrophy		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001271589	SCV001452856	pathogenic	Leber congenital amaurosis	2020-09-16	no assertion criteria provided	clinical testing