Submissions for variant NM_199242.3(UNC13D):c.1055+1G>A

gnomAD frequency: 0.00001  dbSNP: rs754205110

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001383010	SCV001582015	pathogenic	Familial hemophagocytic lymphohistiocytosis 3	2023-10-26	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 12 of the UNC13D gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in UNC13D are known to be pathogenic (PMID: 14622600). This variant is present in population databases (rs754205110, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with familial hemophagocytic lymphohistiocytosis (PMID: 23180437, 29262924). ClinVar contains an entry for this variant (Variation ID: 1070748). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001383010	SCV002020814	pathogenic	Familial hemophagocytic lymphohistiocytosis 3	2019-12-20	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264288	SCV002543122	pathogenic	Autoinflammatory syndrome	2019-09-01	criteria provided, single submitter	clinical testing
Diagnostic Genetics, Severance Hospital, Yonsei University College of Medicine	RCV001383010	SCV003837573	likely pathogenic	Familial hemophagocytic lymphohistiocytosis 3	2023-01-03	criteria provided, single submitter	clinical testing