Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000696279 | SCV000824831 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the DCLRE1C gene. It does not directly change the encoded amino acid sequence of the DCLRE1C protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs750695358, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 574359). 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 is not likely to affect RNA splicing. 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. |
Center for Genomics, |
RCV002060877 | SCV002496094 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency; Histiocytic medullary reticulosis | 2021-07-20 | criteria provided, single submitter | clinical testing | DCLRE1C NM_001033855.1 intron 8 c.678+5G>A: This variant has not been reported in the literature but is present in 0.002% (2/67870) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/10-14934375-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:574359). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Computational prediction tools do not suggest that it alters splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Natera, |
RCV001272389 | SCV001454373 | uncertain significance | Athabaskan severe combined immunodeficiency | 2019-10-28 | no assertion criteria provided | clinical testing |