Submissions for variant NM_199242.3(UNC13D):c.2896C>T (p.Arg966Trp)

dbSNP: rs118049905

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000242082	SCV000317128	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000542743	SCV000406642	likely benign	Familial hemophagocytic lymphohistiocytosis 3	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000542743	SCV000638955	benign	Familial hemophagocytic lymphohistiocytosis 3	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001753732	SCV001985776	uncertain significance	not provided	2020-12-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in the heterozygous state without a second UNC13D variant in individuals with familial hemophagocytic lymphohistiocytosis in the literature (Zhang et al., 2014); these individuals also had a single heterozygous variant in the PRF1 gene suggesting possible digenic inheritance; Identified in the heterozygous state in patients with suspected bleeding disorders in published literature, although one of the patients also had a variant in the RUNX1 gene (Ferrari et al., 2018); This variant is associated with the following publications: (PMID: 24916509, 28399723)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262916	SCV002543174	likely benign	Autoinflammatory syndrome	2021-07-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001753732	SCV004010569	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	UNC13D: BS2