ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5850del (p.Phe1950fs)

dbSNP: rs386834159
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001212861 SCV001384463 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe1950Leufs*15) 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). 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. This premature translational stop signal has been observed in individual(s) with a spectrum of CEP290-related ciliopathy conditions (PMID: 17345604, 17564974, 21866095, 26667666). ClinVar contains an entry for this variant (Variation ID: 56740). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000050153 SCV002555596 pathogenic Meckel syndrome, type 4 2022-05-17 criteria provided, single submitter clinical testing Variant summary: CEP290 c.5850delT (p.Phe1950LeufsX15) 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. Truncations downstream of this position have been classified as pathogenic in ClinVar (e.g. c.7048C>T [p.Gln2350Ter]; c.6798G>A [p.Trp2266Ter]). The variant allele was found at a frequency of 1.8e-05 in 222022 control chromosomes (gnomAD). c.5850delT has been reported in the literature in multiple individuals affected with Meckel Syndrome (e.g. Baala_2007, Tallila_2009), Leber congenital amaurosis (e.g. Perrault_2007) and Nephronophthisis/Joubert Syndrome (e.g. Tory_2007). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002483069 SCV002781105 pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-02-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466925 SCV004216620 pathogenic Bardet-Biedl syndrome 14 2023-06-13 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050153 SCV000082563 probable-pathogenic Meckel syndrome, type 4 no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV001831810 SCV002091860 pathogenic Leber congenital amaurosis 2020-09-25 no assertion criteria provided clinical testing

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