Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048560 | SCV001212573 | uncertain significance | Aicardi-Goutieres syndrome 4 | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 224 of the RNASEH2A protein (p.Val224Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RNASEH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 845489). 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: "Deleterious"; 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. |
| 3billion | RCV001048560 | SCV002573146 | uncertain significance | Aicardi-Goutieres syndrome 4 | 2022-09-01 | criteria provided, single submitter | clinical testing | This missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.61; 3Cnet: 0.38). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |