ClinVar Miner

Submissions for variant NM_183235.3(RAB27A):c.11G>T (p.Gly4Val)

gnomAD frequency: 0.00003  dbSNP: rs539575657
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000795519 SCV000934984 uncertain significance Griscelli syndrome type 2 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4 of the RAB27A protein (p.Gly4Val). This variant is present in population databases (rs539575657, gnomAD 0.04%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 27781387). ClinVar contains an entry for this variant (Variation ID: 642121). 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: "Benign"; Align-GVGD: "Class C65"). 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.
Illumina Laboratory Services, Illumina RCV000795519 SCV001274481 uncertain significance Griscelli syndrome type 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000795519 SCV002495910 uncertain significance Griscelli syndrome type 2 2021-09-09 criteria provided, single submitter clinical testing RAB27A NM_004580.4 exon 2 p.Gly4Val (c.11G>T): This variant has been reported in the literature in 1 individual with hemophagocytic lymphohistiocytosis (Xu 2017 PMID:27781387), and is present in 0.04% (7/18238) of East Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/15-55527122-C-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:642121). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002263986 SCV002542909 uncertain significance Autoinflammatory syndrome 2019-11-01 criteria provided, single submitter clinical testing

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