Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000424806 | SCV000524384 | likely pathogenic | not provided | 2016-02-04 | criteria provided, single submitter | clinical testing | A novel G347E variant that is likely pathogenic was identified in the OCRL gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G347E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G347E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species in a region corresponding to the acyl chain binding site of the enzyme's catalytic domain (Pirruccello and de Camilli 2012). In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Johns Hopkins Genomics, |
RCV001543673 | SCV001762360 | likely pathogenic | Dent disease type 2 | 2021-07-15 | criteria provided, single submitter | clinical testing | This OCRL variant is absent from a large population dataset and has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging. The glycine residue at this position is strongly conserved across the vertebrate species assessed and occurs in a region that corresponds to the acyl chain binding site of the catalytic phosphatase domain of the OCRL protein. This variant is not predicted to affect normal exon 11 splicing, although this has not been confirmed experimentally to our knowledge. We consider this variant to be likely pathogenic. |