Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001314842 | SCV004810423 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2024-04-01 | reviewed by expert panel | curation | The c.50A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Aspartic Acid by Glycine at amino acid 17 (p.Asp17Gly). 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 severe combined immunodeficiency due to DCLRE1C deficiency, based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): PM2_Supporting. |
Labcorp Genetics |
RCV001314842 | SCV001505392 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2020-02-25 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with DCLRE1C-related conditions. This sequence change replaces aspartic acid with glycine at codon 17 of the DCLRE1C protein (p.Asp17Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). |