ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1936C>T (p.Gln646Ter)

gnomAD frequency: 0.00001  dbSNP: rs780225183
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000313260 SCV000329241 pathogenic not provided 2020-05-26 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31974414, 25525159, 17345604, 31734136)
Eurofins Ntd Llc (ga) RCV000313260 SCV000708162 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000636991 SCV000758439 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln646*) 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 Leber congenital amaurosis or nephronophthisis (PMID: 17345604, 26673778). ClinVar contains an entry for this variant (Variation ID: 279751). 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 RCV001075417 SCV001241040 pathogenic Retinal dystrophy 2018-08-06 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001199213 SCV001370235 pathogenic Joubert syndrome 5 2019-02-27 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM1,PM2,PP5.
Fulgent Genetics, Fulgent Genetics RCV002500965 SCV002804870 pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2021-11-13 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463734 SCV004214827 pathogenic Bardet-Biedl syndrome 14 2024-03-06 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833301 SCV002094313 pathogenic Leber congenital amaurosis 2020-12-18 no assertion criteria provided clinical testing

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