Submissions for variant NM_001142800.2(EYS):c.6976C>T (p.Arg2326Ter)

gnomAD frequency: 0.00001  dbSNP: rs1060499783

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454133	SCV000538023	likely pathogenic	Retinitis pigmentosa 25	2015-07-24	criteria provided, single submitter	clinical testing	The c.6976C>T (p.Arg2326*) is a novel nonsense variant in the EYS gene that leads to premature truncation of the protein, causing a disorder where loss of function is a mechanism of disease. Other pathogenic nonsense variants have been described in the EYS gene in several affected individuals, linked to the disease, and reported to be in the same region as this nonsense variant (Littinik et al., 2010 and Iwanami et al., 2012). This p.Arg2326* has not been reported in the three control population databases (Exome Sequencing Project [ESP], 1000 Genomes, and ExAc) and displayed a high CADD score (45). Therefore, this collective evidence supports the classification of the c.6976C>T (p.Arg2326*) as a recessive likely pathogenic variant for Retinitis Pigmentosa-25.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001242418	SCV001415504	pathogenic	not provided	2024-11-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg2326*) in the EYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (no rsID available, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 26161267). ClinVar contains an entry for this variant (Variation ID: 402227). For these reasons, this variant has been classified as Pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001003017	SCV001950270	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Arg2326Ter variant in EYS was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3-P. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Fulgent Genetics, Fulgent Genetics	RCV000454133	SCV002783627	pathogenic	Retinitis pigmentosa 25	2024-03-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000454133	SCV004192940	pathogenic	Retinitis pigmentosa 25	2023-11-14	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003889894	SCV004707454	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV003889894	SCV005070533	pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003017	SCV001161072	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV000454133	SCV002083538	pathogenic	Retinitis pigmentosa 25	2020-09-14	no assertion criteria provided	clinical testing