Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Medical Genetics, |
RCV001375044 | SCV001439256 | likely pathogenic | Meier-Gorlin syndrome 1 | criteria provided, single submitter | research | Analysis of the exome sequencing data showed a novel homozygous sequence variant in ORC1 gene. This variant is predicted as Disease Causing by MutationTaster. This variant is not found in ExAC and 1000G databases. Sanger sequencing confirmed the variation in the proband and the similarly affected female sibling. Mother is heterozygous for the same variation. Father's sample was not available | |
| 3billion | RCV001375044 | SCV005904836 | likely pathogenic | Meier-Gorlin syndrome 1 | 2024-03-07 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.79 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.70 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ORC1 related disorder (ClinVar ID: VCV000982308 /PMID: 35568357). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 35568357). A different missense change at the same codon (p.Arg105Gln) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000030232 /PMID: 21358633). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |