Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000431370 | SCV000536622 | uncertain significance | not specified | 2017-02-01 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL5A2gene. The c.3084 A>G variant has not been published as pathogenic or been reported as benign to our knowledge. It is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Though this variant results in a synonymous amino acid substitution, this variant could be functionally significant at the mRNA level. At the mRNA level, the nucleotide guanine (G) is conserved across most species. However, guanine is wild-type at this nucleotide position in the lamprey species, and in silico splicing algorithms do not predict an impact on splicing. Nevertheless, in the absence of functional or segregation studies the physiological and clinical significance of this variant cannot be determined. Lastly, the c.3084 A>G does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A2 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). |
| Invitae | RCV002056680 | SCV002428340 | likely benign | Ehlers-Danlos syndrome, classic type, 1 | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002319497 | SCV002608786 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |