Submissions for variant NM_001142800.2(EYS):c.4985A>T (p.Asp1662Val)

gnomAD frequency: 0.00192  dbSNP: rs147641443

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153212	SCV000202686	likely benign	not specified	2014-05-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000584981	SCV000693215	uncertain significance	not provided	2017-07-01	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625442	SCV000745362	likely benign	Retinitis pigmentosa 25	2015-09-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000584981	SCV001116323	likely benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164682	SCV001326823	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV000625442	SCV001652728	likely benign	Retinitis pigmentosa 25	2021-05-18	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003888588	SCV004707495	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Natera, Inc.	RCV001164682	SCV001459619	likely benign	Retinitis pigmentosa	2020-01-05	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000584981	SCV001548971	likely benign	not provided		no assertion criteria provided	clinical testing	The EYS p.Asp1662Val variant was not identified in the literature but was identified in dbSNP (ID: rs147641443), ClinVar (classified as likely benign by EGL Genetics and DNA and Cytogenetics Diagnostics Unit, Erasmus Medical Center and as a VUS by CeGaT Praxis fuer Humangenetik Tuebingen) and LOVD 3.0 (classified as likely benign and benign). The variant was also identified in control databases in 390 of 183042 chromosomes (1 homozygous) at a frequency of 0.002131 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (Finnish) in 65 of 18416 chromosomes (freq: 0.00353), European (non-Finnish) in 205 of 73290 chromosomes (freq: 0.002797), Other in 14 of 5366 chromosomes (freq: 0.002609), Latino in 51 of 25484 chromosomes (freq: 0.002001), South Asian in 40 of 22754 chromosomes (freq: 0.001758), African in 13 of 16570 chromosomes (freq: 0.000785) and East Asian in 2 of 12444 chromosomes (freq: 0.000161), but was not observed in the Ashkenazi Jewish population. The p.Asp1662 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and two of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics, Academic Medical Center	RCV000153212	SCV001917854	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965140	SCV004790645	likely benign	EYS-related disorder	2020-12-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).