Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003045587 | SCV004242278 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2024-01-23 | reviewed by expert panel | curation | The c.57C>A (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Phenylalanine by Leucine at amino acid 19 (p.Phe19Leu). This variant is absent from gnomAD v4 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with DCLRE1c-related conditions or in functional studies. Due to insufficient evidence, this variant is classified as a variant of uncertain significance for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): PM2_Supporting. |
Labcorp Genetics |
RCV003045587 | SCV003326594 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 19 of the DCLRE1C protein (p.Phe19Leu). This variant is not present in population databases (gnomAD no frequency). 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: 2107279). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |