Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000254922 | SCV000322475 | pathogenic | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 21699693) |
ARUP Laboratories, |
RCV001002397 | SCV001160318 | pathogenic | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2019-02-20 | criteria provided, single submitter | clinical testing | The c.1651-2A>G variant has been previously identified in the homozygous state in an individual reported to be affected with kyphoscoliotic type Ehlers-Danlos syndrome (Rohrbach. 2011) This variant is found in the non-Finnish European allele frequency of 0.008 % (10/ 126,640 alleles) in the Genome Aggregation Database. This variant disrupts the canonical splice acceptor site of intron 15, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. |
Invitae | RCV001002397 | SCV001578250 | pathogenic | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 15 of the PLOD1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs565513365, gnomAD 0.008%). Disruption of this splice site has been observed in individual(s) with Ehlers-Danlos syndrome, kyphoscoliotic form (PMID: 21699693). ClinVar contains an entry for this variant (Variation ID: 265507). Studies have shown that disruption of this splice site results in skipping of exon 16, but is expected to preserve the integrity of the reading-frame (PMID: 9450904). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002401967 | SCV002704667 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2018-03-26 | criteria provided, single submitter | clinical testing | The c.1651-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 16 in the PLOD1 gene. This alteration has been reported as homozygous in a child with the autosomal recessive kyphoscoliotic type of Ehlers-Danlos syndrome (kEDS), which was previously described as EDS-VIA (Rohrbach M et al. Orphanet J Rare Dis, 2011 Jun;6:46). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
Diagnostic Laboratory, |
RCV000254922 | SCV001744585 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000254922 | SCV001807298 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000254922 | SCV001966652 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |