Submissions for variant NM_000329.3(RPE65):c.1155G>A (p.Thr385=)

gnomAD frequency: 0.00481  dbSNP: rs62653014

Total submissions: 10

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	RCV003460767	SCV004190215	benign	RPE65-related recessive retinopathy	2023-12-22	reviewed by expert panel	curation	NM_000329.3(RPE65):c.1155G>A (p.Thr385=) is a synonymous variant at codon 385. 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). This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.01596, with 704 alleles / 41408 total alleles in the African/African American population, which is higher than the ClinGen LCA / eoRD VCEP BA1 threshold of >0.008 (BA1). In summary, this variant meets the criteria to be classified as benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BA1, BP4, BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
Counsyl	RCV000666107	SCV000790349	likely benign	Leber congenital amaurosis 2; Retinitis pigmentosa 20	2017-03-16	criteria provided, single submitter	clinical testing
Invitae	RCV000666107	SCV001021784	benign	Leber congenital amaurosis 2; Retinitis pigmentosa 20	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001098671	SCV001255054	benign	Leber congenital amaurosis 2	2017-09-15	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001098672	SCV001255055	benign	Retinitis pigmentosa	2017-09-15	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000085153	SCV001945759	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498449	SCV002812433	likely benign	Leber congenital amaurosis 2; Retinitis pigmentosa 20; Retinitis pigmentosa 87 with choroidal involvement	2021-09-27	criteria provided, single submitter	clinical testing
Retina International	RCV000085153	SCV000117290	not provided	not provided		no assertion provided	not provided
Clinical Genetics, Academic Medical Center	RCV001699203	SCV001924910	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000085153	SCV001975891	likely benign	not provided		no assertion criteria provided	clinical testing