ClinVar Miner

Submissions for variant NM_001368894.2(PAX6):c.823C>T (p.Arg275Ter)

dbSNP: rs886041222
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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)
Labcorp Genetics (formerly Invitae), Labcorp RCV000547174 SCV000632670 pathogenic Aniridia 1; Irido-corneo-trabecular dysgenesis 2023-04-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 279862). This premature translational stop signal has been observed in individual(s) with aniridia (PMID: 10234503, 18483559, 22692063, 26661695, 28321846). This variant is not present in population databases (gnomAD no frequency). 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).
Genetics and Molecular Pathology, SA Pathology RCV000496007 SCV000692535 pathogenic Aniridia 1 2015-07-31 criteria provided, single submitter clinical testing
Fulgent Genetics, 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
Wessex Regional Genetics Laboratory, Salisbury District Hospital RCV000496007 SCV001055793 pathogenic Aniridia 1 2019-08-15 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute 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
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL) RCV004545764 SCV003920785 pathogenic PAX6-related disorder 2023-04-27 criteria provided, single submitter research
Juno Genomics, Hangzhou Juno Genomics, Inc 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 PM2_Supporting+PS4+PP4+PVS1
Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics RCV000496007 SCV000584157 pathogenic Aniridia 1 no assertion criteria provided research

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