Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001775223 | SCV002011915 | uncertain significance | Cerebrooculofacioskeletal syndrome 2 | 2021-10-02 | criteria provided, single submitter | clinical testing | It is not observed in the gnomAD v2.1.1 dataset (PM2). Missense changes are a common disease-causing mechanism (PP2). In silico tool predictions suggest no damaging effect of the variant on gene or gene product (REVEL: 0.222; 3Cnet: 0.012, BP4). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV001861131 | SCV002172823 | uncertain significance | not provided | 2022-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 226 of the ERCC2 protein (p.Ala226Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1320050). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003154194 | SCV003843297 | benign | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004040766 | SCV005034855 | uncertain significance | Inborn genetic diseases | 2023-10-15 | criteria provided, single submitter | clinical testing | The p.A226S variant (also known as c.676G>T), located in coding exon 8 of the ERCC2 gene, results from a G to T substitution at nucleotide position 676. The alanine at codon 226 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |