Submissions for variant NM_025114.4(CEP290):c.369del (p.Gln123fs)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008847	SCV001168652	likely pathogenic	not provided	2018-12-20	criteria provided, single submitter	clinical testing	The c.369delA variant in the CEP290 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.369delA variant causes a frameshift starting with codon Glutamine 123, changes this amino acid to a Histidine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Gln123HisfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.369delA variant is observed in 4/24008 (0.017%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). We interpret c.369delA as a likely pathogenic variant.
Invitae	RCV001388565	SCV001589599	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2023-12-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln123Hisfs*2) 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). This variant is present in population databases (rs773622064, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 817646). 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.
Fulgent Genetics, Fulgent Genetics	RCV002481816	SCV002789619	likely pathogenic	Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	2022-03-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467587	SCV004216599	pathogenic	Bardet-Biedl syndrome 14	2024-03-17	criteria provided, single submitter	clinical testing

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