Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001051493 | SCV001215648 | pathogenic | not provided | 2023-05-21 | 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: 847858). This premature translational stop signal has been observed in individual(s) with achromatopsia (PMID: 14757870, 24148654). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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.Glu199Serfs*3) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). |
| Victorian Clinical Genetics Services, |
RCV002471019 | SCV002768273 | pathogenic | Achromatopsia 3 | 2022-02-02 | 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: 0103 - Gain of function and loss of function are known mechanisms of disease in this gene and are associated with achromatopsia 3 (MIM#262300) (PMIDs: 16379026, 23805033). (I) 0106 - This gene is associated with autosomal recessive 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 null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are multiple NMD-predicted variants that have been reported as pathogenic (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported in three individuals with achromatopsia and is classified as pathogenic by a clinical diagnostic laboratory (PMIDs: 14757870, 24148654; ClinVar). (SP) 0906 - Segregation evidence for this variant is inconclusive due to insufficient information (PMID: 14757870). (I) 1007 - No published functional evidence has been identified for this variant. (I) 1201 - Heterozygous variant detected in trans with a second pathogenic heterozygous variant (NM_019098.4(CNGB3): c.1148del; p.(Thr383Ilefs*13)) in a recessive disease in a research setting. (SP) 1205 - This variant has been shown to be maternally inherited in a research setting. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Fulgent Genetics, |
RCV002471019 | SCV002808748 | pathogenic | Achromatopsia 3 | 2022-05-09 | criteria provided, single submitter | clinical testing |