Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV001508821 | SCV001715212 | uncertain significance | not provided | 2021-01-20 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001508821 | SCV003275327 | uncertain significance | not provided | 2022-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 79 of the DGKE protein (p.Gln79Glu). This variant is present in population databases (rs143468147, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DGKE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163610). 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: "Possibly 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. |
Ambry Genetics | RCV002564263 | SCV003535679 | uncertain significance | Inborn genetic diseases | 2021-09-17 | criteria provided, single submitter | clinical testing | The c.235C>G (p.Q79E) alteration is located in exon 2 (coding exon 1) of the DGKE gene. This alteration results from a C to G substitution at nucleotide position 235, causing the glutamine (Q) at amino acid position 79 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Clinical Genomics Laboratory, |
RCV004820883 | SCV004177116 | uncertain significance | Atypical hemolytic-uremic syndrome with DGKE deficiency | 2023-10-27 | criteria provided, single submitter | clinical testing | The DGKE c.235C>G (p.Gln79Glu) variant was identified in a heterozygous state. To our knowledge, this variant has not been reported in the medical literature and is only observed on 64/152,236 alleles in the general population (gnomAD v2.1.1). The variant has been reported in the ClinVar database as a variant of uncertain clinical significance by three laboratories (ClinVar Variation ID: 1163610). Computational predictors are uncertain as to the impact of this variant on DGKE function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the DGKE c.235C>G (p.Gln79Glu) variant is uncertain at this time. |