Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003064491 | SCV003442468 | pathogenic | Familial hemophagocytic lymphohistiocytosis 3 | 2023-07-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2138108). This premature translational stop signal has been observed in individuals with familial hemophagocytic lymphohistiocytosis (PMID: 16278825, 32245292, 32888943). This variant is present in population databases (rs755619812, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Val210Trpfs*39) in the UNC13D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UNC13D are known to be pathogenic (PMID: 14622600). |
| Victorian Clinical Genetics Services, |
RCV003064491 | SCV005400606 | pathogenic | Familial hemophagocytic lymphohistiocytosis 3 | 2024-10-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hemophagocytic lymphohistiocytosis 3 (MIM#608898). (I)) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v4) <0.01 for a recessive condition (7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with hemophagocytic lymphohistiocytosis (PMIDs: 23774160, 21248318, 16278825) and reported as pathogenic in ClinVar. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |