Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000945760 | SCV001091812 | likely benign | Leber congenital amaurosis 13 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001073956 | SCV001239521 | uncertain significance | Retinal dystrophy | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000945760 | SCV002521763 | uncertain significance | Leber congenital amaurosis 13 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.026%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.67; 3Cnet: 0.39). The variant has been reported as likely benign or uncertain significance (ClinVar ID: VCV000767105) and a different missense change at the same codon (p.Ala269Pro) has been reported to be associated with RDH12 related disorder (ClinVar ID: VCV000977815). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230606 | SCV003928711 | likely pathogenic | Leber congenital amaurosis | 2023-04-05 | criteria provided, single submitter | clinical testing | Variant summary: RDH12 c.806C>G (p.Ala269Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00026 in 239508 control chromosomes, predominantly at a frequency of 0.0035 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in RDH12 causing Leber Congenital Amaurosis phenotype (0.0016), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. However, c.806C>G has been reported in the literature in at least eleven, comprehensively genotyped, compound heterozygous individuals of East Asian descent affected with a later-onset mild retinopathy characterized by central macular atrophy (e.g., Xin_2016, Huang_2016, Wang_2022, Kuo_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) have cited the variant with conflicting assessments (VUS, n = 2; likely benign, n = 1). The available evidence suggests this variant represents a hypomorphic allele that causes an later-onset retinopathy phenotype characterized by macular atrophy. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000945760 | SCV004208572 | likely pathogenic | Leber congenital amaurosis 13 | 2024-03-23 | criteria provided, single submitter | clinical testing |