Submissions for variant NM_000329.3(RPE65):c.585C>T (p.Cys195=)

gnomAD frequency: 0.00007  dbSNP: rs571111378

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen	RCV003768911	SCV004697391	likely benign	RPE65-related recessive retinopathy	2024-02-19	reviewed by expert panel	curation	NM_000329.3(RPE65):c.585C>T is a synonymous variant in codon 195, near the center of exon 6. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.001447, with 56 alleles / 30602 total alleles in the South Asian population (with 1 homozygote), which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives a delta score of 0.00, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: BS1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000946377	SCV001092506	benign	Leber congenital amaurosis 2; Retinitis pigmentosa 20	2023-12-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003411909	SCV004128252	likely benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	RPE65: BP4, BP7
Natera, Inc.	RCV001832192	SCV002092766	likely benign	Leber congenital amaurosis	2020-03-02	no assertion criteria provided	clinical testing