Submissions for variant NM_006949.4(STXBP2):c.1375C>T (p.Arg459Trp)

gnomAD frequency: 0.00417  dbSNP: rs142105943

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000406902	SCV000415686	uncertain significance	Familial hemophagocytic lymphohistiocytosis 5	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000406902	SCV001727330	benign	Familial hemophagocytic lymphohistiocytosis 5	2024-01-31	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821006	SCV002066025	benign	not specified	2021-04-19	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263595	SCV002542983	benign	Autoinflammatory syndrome	2020-04-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003884492	SCV004698675	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	STXBP2: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003957699	SCV004768495	benign	STXBP2-related disorder	2020-02-11	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).