Submissions for variant NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter) (rs137852832)

Total submissions: 14

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	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	2017-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000086298	SCV000617621	pathogenic	not provided	2018-05-08	criteria provided, single submitter	clinical testing	The G1890X variant in the CEP290 gene has been reported previously as homozygous and compound heterozygous in multiple individuals from three different families with clinical features of Joubert syndrome, including nephronophthisis (Sayer et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. 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 (Lek et al., 2016). We interpret G1890X as a pathogenic variant.
Invitae	RCV000531295	SCV000634661	pathogenic	Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis	2019-11-05	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. This variant is present in population databases (rs137852832, ExAC 0.04%). This variant is one of the most commonly reported variants in individuals affected with Joubert syndrome (PMID: 16682970, 16682973, 17564967, 21068128, 22693042, 25818971, 26092869), many of whom are homozygous for this variant. It has also been reported in individuals affected with retinitis pigmentosa (PMID: 23591405, 27353947), Leber congenital amaurosis (PMID: 21245082, 22355252), and Meckel syndrome (PMID: 23954617). Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College,Manipal University	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	RCV000001396	SCV001250906	pathogenic	Joubert syndrome 5	2015-11-02	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
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, 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