Submissions for variant NM_025114.4(CEP290):c.1984C>T (p.Gln662Ter)

gnomAD frequency: 0.00005  dbSNP: rs386834152

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000201755	SCV000256385	pathogenic	Joubert syndrome 5	2015-02-23	criteria provided, single submitter	research
Invitae	RCV000685655	SCV000813143	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln662*) 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 (rs386834152, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with CEP290-related conditions (PMID: 17564974, 19466712, 23188109, 23351400). ClinVar contains an entry for this variant (Variation ID: 56733). 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.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376367	SCV001573484	pathogenic	Leber congenital amaurosis 10	2021-04-08	criteria provided, single submitter	research	The CEP290 c.1984C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP1. Based on this evidence we have classified this variant as Pathogenic.
GeneDx	RCV002285263	SCV002575132	pathogenic	not provided	2022-09-23	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 (gnomAD); This variant is associated with the following publications: (PMID: 19764032, 23351400, 28829391, 19466712, 29398085, 23559409, 17564974, 26092869, 25525159, 30718709)
Fulgent Genetics, Fulgent Genetics	RCV002504949	SCV002795818	pathogenic	Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	2021-12-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002285263	SCV004135544	pathogenic	not provided	2022-12-01	criteria provided, single submitter	clinical testing	CEP290: PVS1, PM2
Baylor Genetics	RCV003460645	SCV004214843	pathogenic	Bardet-Biedl syndrome 14	2023-10-22	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050146	SCV000082556	probable-pathogenic	Meckel syndrome, type 4		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787559	SCV000926535	pathogenic	Leber congenital amaurosis	2018-04-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787812	SCV000926822	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Natera, Inc.	RCV000787559	SCV001457920	pathogenic	Leber congenital amaurosis	2020-09-16	no assertion criteria provided	clinical testing