ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1056G>A (p.Glu352=)

gnomAD frequency: 0.15903  dbSNP: rs12145904
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Total submissions: 10
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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 RCV003460765 SCV004190217 benign RPE65-related recessive retinopathy 2023-12-22 reviewed by expert panel curation The NM_000329.3:c.1056G>A variant is a synonymous variant in codon 352 of RPE65, and is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.3944, with 8033 alleles / 19884 total alleles in the East Asian population with 1627 homozygotes, which is higher than the ClinGen LCA / eoRD VCEP BA1 threshold of >0.008 (BA1). The variant does not have a strong prediction of impact at splicing sites according to SpliceAI, which calculates a delta score of 0.12 for splice acceptor gain. Because this score is higher than the ClinGen LCA / eoRD VCEP BP4 / BP7 threshold of <0.1 and lower than the PP3 threshold of >0.2, no in silico predictive codes are met. 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. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
GeneDx RCV000212977 SCV000171376 benign not specified 2011-08-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Preventiongenetics, part of Exact Sciences RCV000212977 SCV000303623 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000395443 SCV000358874 benign Retinitis pigmentosa 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000299398 SCV000358875 benign Leber congenital amaurosis 2 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV001522164 SCV001731648 benign Leber congenital amaurosis 2; Retinitis pigmentosa 20 2024-02-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000299398 SCV001750239 benign Leber congenital amaurosis 2 2021-07-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001533576 SCV001750240 benign Retinitis pigmentosa 87 with choroidal involvement 2021-07-01 criteria provided, single submitter clinical testing
Retina International RCV000085144 SCV000117281 not provided not provided no assertion provided not provided
Natera, Inc. RCV001275329 SCV001460403 benign Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing

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