Submissions for variant NM_183235.3(RAB27A):c.514_518del (p.Gln172fs)

dbSNP: rs767481076

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001090830	SCV001246577	pathogenic	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV000477784	SCV001384103	pathogenic	Griscelli syndrome type 2	2023-10-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln172Asnfs*2) in the RAB27A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acid(s) of the RAB27A protein. This variant is present in population databases (rs767481076, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Griscelli syndrome (PMID: 10835631, 12648328, 23160464, 25312756, 25901543, 30697212). It has also been observed to segregate with disease in related individuals. This variant is also known as 510 del AAGCC. ClinVar contains an entry for this variant (Variation ID: 417958). This variant disrupts a region of the RAB27A protein in which other variant(s) (p.Arg184*) have been determined to be pathogenic (PMID: 10835631, 15475639, 18397837, 19030707, 19953648). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genomics Facility, Ludwig-Maximilians-Universität München	RCV000477784	SCV002073885	pathogenic	Griscelli syndrome type 2	2021-12-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003983090	SCV004800104	pathogenic	RAB27A-related condition	2024-01-19	criteria provided, single submitter	clinical testing	The RAB27A c.514_518del5 variant is predicted to result in a frameshift and premature protein termination (p.Gln172Asnfs*2). In the literature this variant is also referred to as c.510delAAGCC and c. c.510-514delAAGCC. This variant has been reported in the homozygous and presumed homozygous states in individuals from consanguineous families with Griscelli syndrome, familial hemophagocytic lymphohsitiocytosis (FHL), and primary immunodeficiency disorders (Menasche et al. 2000. PubMed ID: 10835631; Sarper et al. 2003. PubMed ID: 12648328; Mamishi et al. 2008. PubMed ID: 18350256; Cetica et al. 2014. PubMed ID: 25312756; Al-Herz et al. 2019. PubMed ID: 30697212). This variant is reported in 0.0053% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in RAB27A are expected to be pathogenic. This variant is interpreted as pathogenic.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477784	SCV000536923	likely pathogenic	Griscelli syndrome type 2	2016-08-26	no assertion criteria provided	research