Submissions for variant NM_001142800.2(EYS):c.490C>T (p.Arg164Ter)

gnomAD frequency: 0.00001  dbSNP: rs794727631

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178152	SCV000230157	pathogenic	not provided	2017-04-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763560	SCV000894391	pathogenic	Retinitis pigmentosa 25	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000178152	SCV000944783	pathogenic	not provided	2024-11-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg164*) 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 (rs794727631, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 22581970, 25753737). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 197186). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000178152	SCV001447698	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000763560	SCV002034844	pathogenic	Retinitis pigmentosa 25	2021-09-22	criteria provided, single submitter	clinical testing	The EYS c.490C>T (p.Arg164Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The variant has been reported in a compound heterozygous state in at least five individuals, including two siblings, affected with retinitis pigmentosa (O'Sullivan et al. 2012; Chen et al. 2015; McGuigan et al. 2017). The variant is reported at a frequency of 0.000008 in the Total population of the Genome Aggregation database (version 2.1.1), though this is based on only two occurrences in a region of good sequence coverage, so the variant is presumed to be rare. Based on the collective evidence, the p.Arg164Ter variant is classified as pathogenic for autosomal recessive retinitis pigmentosa.
3billion, Medical Genetics	RCV000763560	SCV002058243	pathogenic	Retinitis pigmentosa 25	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: VCV000197186, PMID:22581970). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics	RCV000763560	SCV004195217	pathogenic	Retinitis pigmentosa 25	2024-02-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816290	SCV005070987	pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
Genetics and Genomic Medicine Centre, NeuroGen Healthcare, NeuroGen Healthcare	RCV000763560	SCV005873710	pathogenic	Retinitis pigmentosa 25	2021-01-28	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505178	SCV000599152	pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV000763560	SCV002076705	pathogenic	Retinitis pigmentosa 25	2020-07-08	no assertion criteria provided	clinical testing