Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000272947 | SCV000425622 | uncertain significance | Ehlers-Danlos syndrome type 7A | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002229879 | SCV000547877 | benign | Ehlers-Danlos syndrome, classic type, 1 | 2023-09-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000478578 | SCV000571664 | uncertain significance | not provided | 2016-09-14 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL5A2 gene. The V1205A variant has not beenpublished as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V1205A variantwas not observed with any significant frequency in approximately 6,500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in thesepopulations. Nevertheless, the V1205A variant is a conservative amino acid substitution, which is not likely toimpact secondary protein structure as these residues share similar properties. This substitution occurs at a positionthat is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not thevariant is damaging to the protein structure/function. Furthermore, the V1205A does not affect a Glycine residue in aGly-X-Y motif in the triple helical region of the COL5A2 gene, where the majority of pathogenic missense variantsoccur (Stenson et al., 2014; Symoens et al., 2012). However, in contrast to several other collagen genes, relativelyfew pathogenic Glycine substitutions have been reported in COL5A2 in association with Ehlers-Danlos syndrome.Most pathogenic variants in COL5A2 are in-frame splice site changes that cause exon skipping (Symoens et al.,2012). |
| ARUP Laboratories, |
RCV001801811 | SCV002049814 | likely benign | Ehlers-Danlos syndrome, classic type, 2 | 2021-10-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002450901 | SCV002616683 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-29 | criteria provided, single submitter | clinical testing | The p.V1205A variant (also known as c.3614T>C), located in coding exon 50 of the COL5A2 gene, results from a T to C substitution at nucleotide position 3614. The valine at codon 1205 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
| Pittsburgh Clinical Genomics Laboratory, |
RCV004783775 | SCV005397213 | uncertain significance | Telecanthus | 2022-09-21 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (T>C) at coding position 3614 of the COL5A2 gene that results in a valine to alanine amino acid change at residue 1205 of the COL5A2 protein. This is a previously reported variant (ClinVar) that has not been observed in individuals with COL5A2-related illness in the literature, to our knowledge. This variant is present in the gnomAD control population dataset (16 of 282822 alleles or 0.005%). Bioinformatic tools predict that this variant would be tolerated, and the Val1205 residue is moderately conserved across the mammalian species examined. Functiol studies testing the effect of this variant on protein structure or activity have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this to be a variant of uncertain significance. ACMG Criteria: BP4, PM2 |