Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004595855 | SCV005088585 | likely benign | RPE65-related recessive retinopathy | 2024-07-23 | reviewed by expert panel | curation | NM_000329.3(RPE65):c.978G>T (p.Val326=) is a silent variant located near the center of exon 11. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.0003016, with 15 alleles / 30608 total alleles in the South Asian population, which is lower than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 and fails to meet this criterion. The splicing impact predictor SpliceAI gives a delta score of 0.01 for splice donor loss and splice donor gain, 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: BP4 and BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023). |
| Illumina Laboratory Services, |
RCV000403263 | SCV000358871 | uncertain significance | Retinitis pigmentosa | 2018-01-13 | 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, |
RCV000312204 | SCV000358872 | uncertain significance | Leber congenital amaurosis 2 | 2018-01-13 | 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. |
| Labcorp Genetics |
RCV000940201 | SCV001086060 | likely benign | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-12-14 | criteria provided, single submitter | clinical testing |