Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001036395 | SCV001199756 | uncertain significance | Amelocerebrohypohidrotic syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 172 of the ROGDI protein (p.Ala172Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ROGDI-related conditions. ClinVar contains an entry for this variant (Variation ID: 835502). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ce |
RCV002264146 | SCV002545746 | likely benign | not provided | 2022-05-01 | criteria provided, single submitter | clinical testing | ROGDI: BP1 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800663 | SCV005423038 | uncertain significance | not specified | 2024-10-07 | criteria provided, single submitter | clinical testing | Variant summary: ROGDI c.514G>A (p.Ala172Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 179772 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.514G>A has been reported in the literature in an individual from an epilepsy/seizure disorder cohort study (e.g., ATLI_2022). This report does not provide unequivocal conclusions about association of the variant with Amelocerebrohypohidrotic Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 33528079). ClinVar contains an entry for this variant (Variation ID: 835502). Based on the evidence outlined above, the variant was classified as uncertain significance. |