Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002310842 | SCV000318321 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2024-12-02 | criteria provided, single submitter | clinical testing | The c.528+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 5 in the COL3A1 gene. This variant was reported in individual(s) with features consistent with vascular Ehlers-Danlos syndrome (Henneton P et al. Circ Genom Precis Med, 2019 03;12:e001996; external communication; Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Labcorp Genetics |
RCV000464806 | SCV000541788 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2023-06-06 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 263523). This variant has been observed in individuals with clinical features of vascular Ehlers-Danlos syndrome (PMID: 30999998; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 5 of the COL3A1 gene. It does not directly change the encoded amino acid sequence of the COL3A1 protein. It affects a nucleotide within the consensus splice site. |
Ce |
RCV000512993 | SCV000609013 | uncertain significance | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000512993 | SCV000695376 | uncertain significance | not provided | 2016-12-25 | criteria provided, single submitter | clinical testing | Variant summary: c.528+5G>A in COL3A1 gene is an intronic change that involves a highly conserved nucleotide. 5/5 programs in Alamut predict that this variant eliminates the donor splice site, however no functional studies supporting this notion were published at the time of evaluation. The variant is absent from control population dataset of ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as VUS by a reputable database/clinical laboratory. Considering all, due to the lack of sufficient clinical information on carriers and absence of functional studies the variant has been currently classified as a variant of uncertain significance until additional information becomes available. |
Gene |
RCV000512993 | SCV004022891 | likely pathogenic | not provided | 2024-09-04 | criteria provided, single submitter | clinical testing | Reported in an individual with clinical features of vEDS (PMID: 30999998, 30919682); Not observed at significant frequency in large population cohorts (gnomAD); Intronic variant directly or indirectly altering the +5 splice site in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; This variant is associated with the following publications: (PMID: 30919682, 30999998, 35571021) |
Genome |
RCV001535582 | SCV001749577 | not provided | Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome | no assertion provided | phenotyping only | Variant interpreted as Likely pathogenic and reported on 07-29-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |