Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000011604 | SCV000753971 | pathogenic | Lowe syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 10857). This variant is also known as c.2746C>T. This premature translational stop signal has been observed in individuals with Lowe syndrome (PMID: 8504307). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg844*) in the OCRL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OCRL are known to be pathogenic (PMID: 19390221, 21031565, 22381590). |
| Gene |
RCV001588808 | SCV001823431 | pathogenic | not provided | 2019-05-31 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 58 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21031565, 25525159, 8504307) |
| Victorian Clinical Genetics Services, |
RCV000011604 | SCV002768787 | pathogenic | Lowe syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, 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 Lowe syndrome (MIM#309000) and Dent disease 2 (MIM#300555). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 – Other truncating variants downstream to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported as pathogenic (ClinVar, PMID: 21031565). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic and observed in patients with Lowe syndrome (ClinVar, PMID: 21031565). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific phenotype match for this individual. (SP) 1205 - This variant has been shown to be maternally inherited (VCGS #20G001940). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV002496327 | SCV002808936 | pathogenic | Dent disease type 2; Lowe syndrome | 2021-09-28 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000011604 | SCV000031836 | pathogenic | Lowe syndrome | 1993-04-01 | no assertion criteria provided | literature only |