Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003769057 | SCV004697422 | uncertain significance | RPE65-related recessive retinopathy | 2024-02-20 | reviewed by expert panel | curation | NM_000329.3(RPE65):c.1129-5C>T is an intronic variant -5 from exon 11 and has only been reported once to date in published literature. There is no computational predictor REVEL score for the variant NM_000329.3(RPE65):c.1129-5C>T. The splicing impact predictor SpliceAI gives a delta score of 0, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4 met). This variant is present in gnomAD v.2.1.1 at a Grpmax allele frequency of 0.00003454, with 11 alleles/127858 total alleles in the European (non-Finnish) population, which is lower than the ClinGen LCA/eoRD VCEP PM2_supporting threshold of <0.0002 (PM2_Supporting). A published report (PMID:35569774) described a proband with recessive RP (proband P7) heterozygous for the c.1129-5C>T variant but failed to find any additional variants in RPE65. (PM3_not met). In summary, this variant meets the criteria to be classified as a variant of uncertain significance (VUS) for RPE65-related recessive retinopathy due to insufficient evidence based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP with a total combined score of 0: BP4, PM2_supporting. (VCEP specifications version 1.0.0; date of approval 09/21/2023). |
Illumina Laboratory Services, |
RCV001098675 | SCV001255058 | uncertain significance | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001098676 | SCV001255059 | uncertain significance | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV001492656 | SCV001697273 | likely benign | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-12-05 | criteria provided, single submitter | clinical testing |