Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002028474 | SCV002286413 | likely pathogenic | Severe combined immunodeficiency due to DCLRE1C deficiency | 2022-12-31 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the DCLRE1C 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 DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). Disruption of this splice site has been observed in individual(s) with severe combined immunodeficiency (PMID: 34220820). ClinVar contains an entry for this variant (Variation ID: 1496282). Studies have shown that disruption of this splice site is associated with altered splicing resulting in unknown protein product impact (PMID: 34220820). 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. |