Submissions for variant NM_001142800.2(EYS):c.8133_8137del (p.Phe2712fs)

dbSNP: rs751629543

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674390	SCV000799715	likely pathogenic	Retinitis pigmentosa 25	2018-05-02	criteria provided, single submitter	clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000674390	SCV001156413	pathogenic	Retinitis pigmentosa 25	2019-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000674390	SCV001157960	pathogenic	Retinitis pigmentosa 25	2018-11-12	criteria provided, single submitter	clinical testing	The EYS c.8133_8137delCTTTC; p.Phe2712fs variant (rs751629543), also known as c.8196_8200delCTTTC p.F2733Cfs*33 based on NM_001292009.1, is published in the medical literature in a family with autosomal recessive retinitis pigmentosa (Arai 2015). The variant is listed in the ClinVar database (Variation ID: 558163) and in the general population with an allele frequency of 0.006% (9/148188 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 5 nucleotides so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, this variant is predicted to cause loss of a critical functional domain (Hosono 2012). Considering available information, this variant is predicted to be pathogenic. References: Arai Y et al. Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations. J Ophthalmol. 2015;2015:819760 Hosono K et al. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population. PLoS One. 2012;7(2):e31036
Labcorp Genetics (formerly Invitae), Labcorp	RCV001060857	SCV001225572	pathogenic	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe2712Cysfs*33) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 433 amino acid(s) of the EYS protein. This variant is present in population databases (rs751629543, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 26161267, 30153090). ClinVar contains an entry for this variant (Variation ID: 558163). This variant disrupts a region of the EYS protein in which other variant(s) (p.Thr3038Ilefs*4 and p.Asn3061Thrfs*3) have been determined to be pathogenic (PMID: 20333770, 21069908). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000674390	SCV001573646	pathogenic	Retinitis pigmentosa 25	2021-04-08	criteria provided, single submitter	research	The EYS c.8133_8137del 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, PM3. Based on this evidence we have classified this variant as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000674390	SCV002776378	pathogenic	Retinitis pigmentosa 25	2024-02-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000674390	SCV004192924	pathogenic	Retinitis pigmentosa 25	2024-02-22	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003889964	SCV004707416	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Natera, Inc.	RCV001271839	SCV001453304	pathogenic	Autosomal recessive retinitis pigmentosa	2020-09-16	no assertion criteria provided	clinical testing