Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV005200794 | SCV005835758 | likely pathogenic | Severe combined immunodeficiency due to DCLRE1C deficiency | 2024-03-11 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the DCLRE1C mRNA. The next in-frame methionine is located at codon 8. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with severe combined immunodeficiency (PMID: 15731174, 24144642, 25917813). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as M1V. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon does not substantially affect DCLRE1C function (PMID: 25917813). 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. |