Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000804952 | SCV000944892 | uncertain significance | Familial acute necrotizing encephalopathy | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1786 of the RANBP2 protein (p.Asp1786Tyr). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 649908). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. This variant is present in population databases (rs753417427, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. |
| Ambry Genetics | RCV004028201 | SCV004934409 | uncertain significance | not specified | 2024-01-04 | criteria provided, single submitter | clinical testing | The c.5356G>T (p.D1786Y) alteration is located in exon 20 (coding exon 20) of the RANBP2 gene. This alteration results from a G to T substitution at nucleotide position 5356, causing the aspartic acid (D) at amino acid position 1786 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |