Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001390411 | SCV001592137 | pathogenic | Leber congenital amaurosis 3 | 2022-03-10 | 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: 1076482). This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 21310915). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs777346333, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Leu89Lysfs*4) in the SPATA7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPATA7 are known to be pathogenic (PMID: 19268277, 22334370, 23847139, 26047050, 26261414). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001844288 | SCV002103936 | pathogenic | Leber congenital amaurosis | 2022-02-18 | criteria provided, single submitter | clinical testing | Variant summary: SPATA7 c.265_268delCTCA (p.Leu89LysfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have not been observed at our laboratory but have been observed in the HGMD database. The variant allele was found at a frequency of 8e-06 in 250644 control chromosomes. c.265_268delCTCA has been reported in the literature in individuals affected with Leber Congenital Amaurosis and Hereditary Retinal Degeneration (example, Mackay_2011, Xiao_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV001390411 | SCV000045080 | pathogenic | Leber congenital amaurosis 3 | 2011-05-09 | no assertion criteria provided | literature only |