Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799311 | SCV000938968 | uncertain significance | Familial acute necrotizing encephalopathy | 2023-07-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 645263). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. This variant is present in population databases (rs142454773, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1129 of the RANBP2 protein (p.Asp1129Glu). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509541 | SCV002819796 | uncertain significance | not specified | 2022-12-24 | criteria provided, single submitter | clinical testing | Variant summary: RANBP2 c.3387T>G (p.Asp1129Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250500 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3387T>G in individuals affected with Familial Acute Necrotizing Encephalopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |