Submissions for variant NM_001142800.2(EYS):c.6794del (p.Pro2265fs)

dbSNP: rs758109813

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724856	SCV000332067	pathogenic	not provided	2015-06-12	criteria provided, single submitter	clinical testing
Counsyl	RCV000340528	SCV000795358	pathogenic	Retinitis pigmentosa 25	2017-11-03	criteria provided, single submitter	clinical testing
Invitae	RCV000724856	SCV000963324	pathogenic	not provided	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro2265Glnfs*46) 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 (rs758109813, gnomAD 0.3%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 25412400, 29550188). ClinVar contains an entry for this variant (Variation ID: 281325). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001073786	SCV001239347	pathogenic	Retinal dystrophy	2018-01-22	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000340528	SCV001573427	pathogenic	Retinitis pigmentosa 25	2021-04-08	criteria provided, single submitter	research	The EYS c.6794del 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, PS1. Based on this evidence we have classified this variant as Pathogenic.
GeneDx	RCV000724856	SCV001765187	pathogenic	not provided	2021-11-02	criteria provided, single submitter	clinical testing	Frameshift 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: 20537394, 32795431, 20333770, 25412400, 29550188, 32141364, 31589614)
3billion	RCV000340528	SCV002058554	pathogenic	Retinitis pigmentosa 25	2022-01-03	criteria provided, single submitter	clinical testing	Frameshift: 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). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000275, PM2_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000281325, PMID:20333770). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity	RCV000340528	SCV003823888	pathogenic	Retinitis pigmentosa 25	2022-01-27	criteria provided, single submitter	clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV001272872	SCV004030406	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Baylor Genetics	RCV000340528	SCV004192865	pathogenic	Retinitis pigmentosa 25	2023-10-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001272872	SCV004804433	pathogenic	Retinitis pigmentosa	2024-01-11	criteria provided, single submitter	clinical testing	Variant summary: EYS c.6794delC (p.Pro2265GlnfsX46) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00018 in 157910 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in EYS causing Retinitis Pigmentosa (0.00018 vs 0.0034), allowing no conclusion about variant significance. c.6794delC has been reported in the literature in individuals affected with Retinitis Pigmentosa (e.g. Consugar_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 281325). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc.	RCV001272872	SCV001455288	pathogenic	Retinitis pigmentosa	2020-09-16	no assertion criteria provided	clinical testing