Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000606194 | SCV000711776 | pathogenic | Griscelli syndrome | 2016-02-23 | criteria provided, single submitter | clinical testing | The p.Arg50LysfsX35 variant in RAB27A has been reported in 4 individuals with Gr iscelli syndrome type 2 in the homozygous state (Menasche 2000). This variant ha s also been identified in 2/66,636 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Although this variant has be en seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The p.Arg50LysfsX35 variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 50 and leads to a premature termination codon 35 amino acids downstream . This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic for Gri scelli syndrome type 2 in an autosomal recessive manner based upon case studies, low population frequency and functional prediction. |
| Labcorp Genetics |
RCV001860238 | SCV002196233 | pathogenic | Griscelli syndrome type 2 | 2024-12-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg50Lysfs*35) in the RAB27A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAB27A are known to be pathogenic (PMID: 10835631, 23160464). This variant is present in population databases (rs770601673, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with Griscelli syndrome (PMID: 10835631, 12148598). ClinVar contains an entry for this variant (Variation ID: 504894). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001860238 | SCV002808771 | pathogenic | Griscelli syndrome type 2 | 2022-05-25 | criteria provided, single submitter | clinical testing | |
| Genomic Medicine Center of Excellence, |
RCV001860238 | SCV005375263 | pathogenic | Griscelli syndrome type 2 | 2024-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (GRCh38; NM_183236.3:c.149del:p.Arg50LysfsTer35) in the RAB27A protein. This alteration is expected to result in loss of function by premature termination codon resulting in protein truncation, or nonsense-mediated mRNA decay. This alteration is interpreted as disease-causing mutation, a commonly known mechanism for disease. Not observed at significant frequency in large population cohorts (gnomAD). This variant has a strong Conservation score. ClinVar contains an entry for this variant (Variation ID: 504894). This variant is associated with the following publications: PubMed: 12148598, 10835631, 23160464, 16551969, 18350256, 19953648, 26684649 In summary, this variant meets our criteria for classification as pathogenic based on the evidence outlined. |