Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Juno Genomics, |
RCV004796146 | SCV005417507 | pathogenic | Aniridia 1; Foveal hypoplasia 1; Coloboma of optic nerve; Autosomal dominant keratitis; Isolated optic nerve hypoplasia; Irido-corneo-trabecular dysgenesis; Coloboma, ocular, autosomal dominant | criteria provided, single submitter | clinical testing | Absent from controls (or at extremely low frequency if recessive) in Genome Aggregation Database, Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.;The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls.;Patient's phenotype or family history is highly specific for a disease with a single genetic etiology.;Null variant in a gene where loss of function (LOF) is a known mechanism of disease. | |
| Neurometabolic Diseases Laboratory, |
RCV004545764 | SCV003920785 | pathogenic | PAX6-related disorder | 2023-04-27 | criteria provided, single submitter | research | |
| Victorian Clinical Genetics Services, |
RCV000496007 | SCV002769300 | pathogenic | Aniridia 1 | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with PAX6-related conditions. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by multiple clinical laboratories in ClinVar. (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Wessex Regional Genetics Laboratory, |
RCV000496007 | SCV001055793 | pathogenic | Aniridia 1 | 2019-08-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000762839 | SCV000893198 | pathogenic | Aniridia 1; Foveal hypoplasia 1; Coloboma of optic nerve; Autosomal dominant keratitis; Isolated optic nerve hypoplasia; Irido-corneo-trabecular dysgenesis; 11p partial monosomy syndrome; Congenital ocular coloboma | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Genetics and Molecular Pathology, |
RCV000496007 | SCV000692535 | pathogenic | Aniridia 1 | 2015-07-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000547174 | SCV000632670 | pathogenic | Aniridia 1; Irido-corneo-trabecular dysgenesis | 2025-03-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg261*) in the PAX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAX6 are known to be pathogenic (PMID: 12634864). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 10234503, 18483559, 22692063, 26661695, 28321846). Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this PAX6 variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 10,718 individuals referred to our laboratory for PAX6 testing. ClinVar contains an entry for this variant (Variation ID: 279862). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000272207 | SCV000329452 | pathogenic | not provided | 2021-03-18 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33120723, 31861090, 22692063, 18483559, 28321846, 29618921, 12634864, 26661695, 10234503, 25525159, 32360764) |
| Laboratory of Genetic Epidemiology, |
RCV000496007 | SCV000584157 | pathogenic | Aniridia 1 | no assertion criteria provided | research |