Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001068009 | SCV001233096 | uncertain significance | Aicardi-Goutieres syndrome 4 | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 76 of the RNASEH2A protein (p.Arg76Gln). This variant is present in population databases (rs747608935, gnomAD 0.02%). 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: 861478). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RNASEH2A protein function. 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 | RCV003160558 | SCV003868754 | uncertain significance | Inborn genetic diseases | 2023-02-17 | criteria provided, single submitter | clinical testing | The c.227G>A (p.R76Q) alteration is located in exon 3 (coding exon 3) of the RNASEH2A gene. This alteration results from a G to A substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Neuberg Centre For Genomic Medicine, |
RCV001068009 | SCV005439001 | uncertain significance | Aicardi-Goutieres syndrome 4 | 2023-07-22 | criteria provided, single submitter | clinical testing | The observed missense variant c.227G>Ap.Arg76Gln in RNASEH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with 0.002% allele frequency in gnomAD Exomes. It has been submitted to ClinVar as Uncertain Significance. The amino acid Arg at position 76 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence Polyphen-probably damaging, SIFT-damaging and Mutation Taster-disease causing predict a damaging effect on protein structure and function for this variant. The reference amino acid p.Arg76Gln in RNASEH2A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant, the molecular diagnosis is not confirmed |