Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001355998 | SCV001551044 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | The ORC1 p.P231Qfs*12 variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs1362231446) and in control databases in 1 of 251390 chromosomes at a frequency of 0.000003978 (Genome Aggregation Database March 6, 2019, v2.1.1). The c.692delC variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 231 and leads to a premature stop codon 12 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the ORC1 gene have been reported as a mechanism of disease in autosomal recessive Meier-Gorlin syndrome and is the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state (de Munnik_2012_PMID:22333897). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |