ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)

gnomAD frequency: 0.00006  dbSNP: rs137852832
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Total submissions: 31
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000114202 SCV000147755 pathogenic Meckel-Gruber syndrome 2013-07-22 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000086298 SCV000202411 pathogenic not provided 2014-05-01 criteria provided, single submitter clinical testing
UW Hindbrain Malformation Research Program, University of Washington RCV000001396 SCV000256366 pathogenic Joubert syndrome 5 2015-02-23 criteria provided, single submitter research
Fulgent Genetics, Fulgent Genetics RCV000515339 SCV000611257 pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-20 criteria provided, single submitter clinical testing
GeneDx RCV000086298 SCV000617621 pathogenic not provided 2022-01-04 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; This variant is associated with the following publications: (PMID: 25937446, 23591405, 23954617, 21866095, 25818971, 16682973, 22355252, 29518907, 29398085, 26092869, 30718709, 25525159, 32139166, 27353947, 16682970, 22693042, 29620724, 28559085, 31411728, 31734136, 31589614, 21245082, 21068128, 20690115, 17564967, 17345604, 16909394, 31091803, 31488071, 31346239, 30446612, 29298421, 30114557, 26862157, 26729329, 27081510, 23847139, 19778711)
Invitae RCV000531295 SCV000634661 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly1890*) 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 (rs137852832, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Joubert syndrome, Leber congenital amaurosis, and/or retinitis pigmentosa (PMID: 16682970, 16682973, 17564967, 21068128, 21245082, 22355252, 22693042, 23591405, 23954617, 25818971, 26092869, 27353947). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1333). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001000092 SCV000930045 pathogenic Meckel syndrome, type 4 criteria provided, single submitter research
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV001002714 SCV001156390 pathogenic Senior-Loken syndrome 6; Joubert syndrome 5 2019-02-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073790 SCV001239352 pathogenic Retinal dystrophy 2018-02-28 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV001836688 SCV001250906 pathogenic Abnormality of the nervous system 2021-07-10 criteria provided, single submitter clinical testing
Pathology and Clinical Laboratory Medicine, King Fahad Medical City RCV000001396 SCV001438883 pathogenic Joubert syndrome 5 criteria provided, single submitter clinical testing
Pathology and Clinical Laboratory Medicine, King Fahad Medical City RCV001261607 SCV001438891 pathogenic Meckel syndrome, type 6 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000001396 SCV001443021 pathogenic Joubert syndrome 5 2023-01-03 criteria provided, single submitter clinical testing This variant was identified as homozygous._x000D_ Criteria applied: PVS1, PM3_VSTR, PM2_SUP, PP4
Baylor Genetics RCV000001396 SCV001523407 pathogenic Joubert syndrome 5 2020-06-01 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Genomics England Pilot Project, Genomics England RCV001542773 SCV001760312 likely pathogenic Bardet-Biedl syndrome 14 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000086298 SCV002017019 pathogenic not provided 2023-07-19 criteria provided, single submitter clinical testing
3billion RCV000001396 SCV002059088 pathogenic Joubert syndrome 5 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000001333, PMID:16682973). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000095, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Suma Genomics RCV001815157 SCV002062078 pathogenic COG7 congenital disorder of glycosylation criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000001396 SCV002072977 pathogenic Joubert syndrome 5 criteria provided, single submitter clinical testing The stop gained p.G1890* in CEP290 (NM_025114.4) has been reported has been reported previously as homozygous and compound heterozygous in multiple individuals and is one of the most commonly reported variants in Joubert syndrome (Sayer et al,Bachmann-Gagescu R et al). This variant is predicted to cause loss of normal protein function through protein truncation. The G1890X variant is observed in 6/14472 (0.04%) alleles from individuals of South Asian background, in the ExAC dataset, and no individuals were reported to be homozygous. For these reasons, this variant has been classified as Pathogenic
Suma Genomics RCV001836689 SCV002097332 pathogenic Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 criteria provided, single submitter clinical testing
Baylor Genetics RCV003147273 SCV003836349 pathogenic CEP290-Related Disorders 2022-05-13 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital RCV000001396 SCV004045776 pathogenic Joubert syndrome 5 2023-10-19 criteria provided, single submitter clinical testing This homozygous termination variant identified in 2 year male with GDD, and breathing difficulties with hypotonia, nystagmus, retinal dystrophy. MRI Brain revealed Molar Tooth sign suggestive of Joubert Syndrome. Family history of female sibling expired 10 hours of life with respiratory distress. This nucleotide change has an allele frequency of 0.0098% in gnomAD aggregate database [PM2], In-silico prediction tools [MutationTaster] predict a deleterious nature of this variant. This variant is submitted to clinvar database multiple times with an interpretation "Pathogenic/Likely Pathogenic". Clinvar variation id [1333] [PP5]. PMID [26092869] Based on the available evidences and the clinical phenotype in our case, this variant is classified as "Pathogenic".
Preventiongenetics, part of Exact Sciences RCV003415616 SCV004113819 pathogenic CEP290-related condition 2023-04-27 criteria provided, single submitter clinical testing The CEP290 c.5668G>T variant is predicted to result in premature protein termination (p.Gly1890*). This variant is one of the most common pathogenic variants detected in CEP290 and has been documented as causative for Joubert syndrome (Sayer et al. 2006. PubMed ID: 16682973; Valente et al. 2006. PubMed ID: 16682970; Brancati et al. 2007. PubMed ID: 17564967; Bachmann-Gagescu et al. 2015. PubMed ID: 26092869). Different chain-terminating variants in CEP290 have been reported in patients with Meckel-Gruber syndrome (Baala et al. 2007. PubMed ID: 17564974; Frank et al. 2008. PubMed ID: 17705300) and Bardet-Biedl syndrome (Leitch et al. 2008. PubMed ID: 18327255). This variant is reported in 0.020% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88471040-C-A). Nonsense variants in CEP290 are expected to be pathogenic, and this variant has been classified as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1333/). Given all the evidence, we interpret c.5668G>T (p.Gly1890*) as pathogenic.
Baylor Genetics RCV001542773 SCV004214854 pathogenic Bardet-Biedl syndrome 14 2023-10-18 criteria provided, single submitter clinical testing
OMIM RCV000001396 SCV000021546 pathogenic Joubert syndrome 5 2007-07-01 no assertion criteria provided literature only
Retina International RCV000086298 SCV000118444 not provided not provided no assertion provided not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787813 SCV000926823 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000001396 SCV001133222 likely pathogenic Joubert syndrome 5 2019-09-26 no assertion criteria provided clinical testing
Natera, Inc. RCV001276487 SCV001462866 pathogenic Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000086298 SCV001932642 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000086298 SCV001957713 pathogenic not provided no assertion criteria provided clinical testing

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