ClinVar Miner

Submissions for variant NM_199242.3(UNC13D):c.1727+1G>A

gnomAD frequency: 0.00001  dbSNP: rs754882266
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000640104 SCV000761692 likely pathogenic Familial hemophagocytic lymphohistiocytosis 3 2024-06-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 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 (rs754882266, gnomAD 0.006%). 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: 533098). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV000640104 SCV002020817 pathogenic Familial hemophagocytic lymphohistiocytosis 3 2020-03-25 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000640104 SCV004047522 likely pathogenic Familial hemophagocytic lymphohistiocytosis 3 criteria provided, single submitter clinical testing The splice site c.1727+1G>A variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1727+1G>A variant is novel (not in any individuals) in 1000 Genomes and has an allele frequency of 0.0008% in gnomAD database. This variant has been reported to the ClinVar database as Likely Pathogenic. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. No significant variant in UNC13D gene has been observed in the spouse.

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