Submissions for variant NM_000329.3(RPE65):c.643+5G>A

dbSNP: rs61752890

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844037	SCV002103453	uncertain significance	not specified	2022-02-22	criteria provided, single submitter	clinical testing	Variant summary: RPE65 c.643+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251096 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.643+5G>A has been reported in the literature in a heterozygous individual affected with inherited retinal degeneration without evidence for causality (example: Thompson_2000). This report does not provide unequivocal conclusions about association of the variant with Leber Congenital Amaurosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Retina International	RCV000085212	SCV000117349	not provided	not provided		no assertion provided	not provided