Submissions for variant NM_001142800.2(EYS):c.9286_9295del (p.Val3096fs)

dbSNP: rs770748359

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726393	SCV000344348	pathogenic	not provided	2016-08-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000367405	SCV000791383	likely pathogenic	Retinitis pigmentosa 25	2017-05-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000726393	SCV000942225	pathogenic	not provided	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val3096Leufs*28) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the EYS protein. This variant is present in population databases (rs770748359, gnomAD 0.3%). This premature translational stop signal has been observed in individuals with EYS-related conditions (PMID: 24474277, 26261414, 29550188). ClinVar contains an entry for this variant (Variation ID: 289906). This variant disrupts the C-terminus of the EYS protein. Other variant(s) that disrupt this region (p.Tyr3135*, p.Asn3123Lysfs*3) have been observed in individuals with EYS-related conditions (PMID: 18976725, 20333770). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001074689	SCV001240282	pathogenic	Retinal dystrophy	2019-03-23	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000726393	SCV001447697	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000367405	SCV001573555	likely pathogenic	Retinitis pigmentosa 25	2021-04-08	criteria provided, single submitter	research	The EYS c.9286_9295del 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, PP1. Based on this evidence we have classified this variant as Likely Pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001003010	SCV001950253	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Val3096LeufsTer28 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, PP3. 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.
GeneDx	RCV000726393	SCV002032575	pathogenic	not provided	2023-12-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in abnormal protein length as the last 49 amino acids are replaced with 27 different amino acids, and other similar variants have been reported in HGMD; This variant is associated with the following publications: (PMID: 31980526, 26261414, 24474277, 31589614, 32037395, 29550188)
Fulgent Genetics, Fulgent Genetics	RCV000367405	SCV002809834	likely pathogenic	Retinitis pigmentosa 25	2022-04-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000367405	SCV004183550	pathogenic	Retinitis pigmentosa 25	2024-03-28	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003010	SCV001161065	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV001003010	SCV001453299	pathogenic	Retinitis pigmentosa	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751444	SCV005348882	pathogenic	EYS-related disorder	2024-09-26	no assertion criteria provided	clinical testing	The EYS c.9286_9295del10 variant is predicted to result in a frameshift and premature protein termination (p.Val3096Leufs*28). This variant has been reported in the homozygous or compound heterozygous state in several individuals with retinitis pigmentosa (see for example, Beryozkin et al. 2014. PubMed ID: 24474277; Zampaglione et al. 2020. PubMed ID: 32037395; Tracewska et al 2021. PubMed ID: 34321860; Zampaglione et al. 2021. PubMed ID: 34906470; Weisschuh et al. 2024. PubMed ID: 37734845; Sengillo et al. 2018. PubMed ID: 29550188). This variant is reported in 0.25% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Frameshift variants in EYS are expected to be pathogenic. This variant is interpreted as pathogenic.