Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000685947 | SCV000813448 | uncertain significance | Griscelli syndrome type 2 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 92 of the RAB27A protein (p.Ala92Val). This variant is present in population databases (rs137960099, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with RAB27A-related conditions. ClinVar contains an entry for this variant (Variation ID: 566199). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAB27A 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. |
| Genome Diagnostics Laboratory, |
RCV002263930 | SCV002542921 | uncertain significance | Autoinflammatory syndrome | 2021-06-04 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000685947 | SCV003841444 | uncertain significance | Griscelli syndrome type 2 | 2023-02-23 | 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: 0.005%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.67; 3Cnet: 0.34). Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline. |