Submissions for variant NM_199242.3(UNC13D):c.2091+2_2091+3dup

gnomAD frequency: 0.00001  dbSNP: rs778809705

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001214824	SCV001386529	uncertain significance	Familial hemophagocytic lymphohistiocytosis 3	2022-07-06	criteria provided, single submitter	clinical testing	This sequence change falls in intron 22 of the UNC13D gene. It does not directly change the encoded amino acid sequence of the UNC13D protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778809705, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with UNC13D-related conditions. ClinVar contains an entry for this variant (Variation ID: 944427). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003883578	SCV004703495	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	UNC13D: PM2, BP4