ClinVar

Description

Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 153716 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 1.17 fold of the estimated maximal expected allele frequency for a pathogenic variant in EYS causing Retinitis Pigmentosa phenotype (0.0034), strongly suggesting that the variant is benign. c.5510G>C has been reported in the literature in individuals affected with Retinitis Pigmentosa, however it is often observed in the heterozygous state without a variant reported in the second allele and in several studies the variant was considered to be a polymorphism (example Audo_2010, Eisenberger_2013, Wang_2014, Perez-Carro_2016). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. Six ClinVar submitters have provided assessments for this variant after 2014. Two classified the variant as benign, three as likely benign, and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign.