Submissions for variant NM_001142800.2(EYS):c.9405T>A (p.Tyr3135Ter)

gnomAD frequency: 0.00006  dbSNP: rs137853190

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000593252	SCV000709692	likely pathogenic	not provided	2015-10-21	criteria provided, single submitter	clinical testing	The Y3156X likely pathogenic variant in the EYS gene has been reported previously in the homozygous state in two unrelated families with autosomal recessive retinitis pigmentosa (Collin et al., 2008). This variant is predicted to cause loss of normal protein function through protein truncation. Furthermore, the Y3156X variant was not observed in approximately 2,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret Y3156X as a likely pathogenic variant
Counsyl	RCV000000568	SCV000796512	likely pathogenic	Retinitis pigmentosa 25	2017-12-19	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000000568	SCV000894389	likely pathogenic	Retinitis pigmentosa 25	2018-10-31	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001075385	SCV001241007	pathogenic	Retinal dystrophy	2018-07-10	criteria provided, single submitter	clinical testing
Invitae	RCV000593252	SCV001587473	pathogenic	not provided	2024-01-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr3135*) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 10 amino acid(s) of the EYS protein. This variant is present in population databases (rs137853190, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with EYS-related conditions (PMID: 18976725, 29159838, 30337596, 31074760). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.9468T>A;p.Y3156X. ClinVar contains an entry for this variant (Variation ID: 538). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000593252	SCV001747467	pathogenic	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001723527	SCV001950254	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Tyr3135Ter 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.
Revvity Omics, Revvity	RCV000000568	SCV002024538	likely pathogenic	Retinitis pigmentosa 25	2019-12-11	criteria provided, single submitter	clinical testing
Mendelics	RCV000000568	SCV002519620	pathogenic	Retinitis pigmentosa 25	2022-05-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000000568	SCV004192853	pathogenic	Retinitis pigmentosa 25	2024-03-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003914789	SCV004736726	pathogenic	EYS-related disorder	2024-03-01	criteria provided, single submitter	clinical testing	The EYS c.9405T>A variant is predicted to result in premature protein termination (p.Tyr3135*). This variant has been reported to be causative for autosomal recessive retinitis pigmentosa (Collin et al. 2008. PubMed ID: 18976725; Ezquerra-Inchausti et al. 2018. PubMed ID: 30337596; Messchaert et al. 2018. PubMed ID: 29159838). This variant is reported in 0.0050% of alleles in individuals of Latino descent in gnomAD. Nonsense variants in EYS are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM	RCV000000568	SCV000020717	pathogenic	Retinitis pigmentosa 25	2008-11-01	no assertion criteria provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000593252	SCV001959664	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000593252	SCV001975574	pathogenic	not provided		no assertion criteria provided	clinical testing