ClinVar Miner

Submissions for variant NM_181741.4(ORC4):c.521A>G (p.Tyr174Cys) (rs387906847)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000023230 SCV000248410 likely pathogenic Meier-Gorlin syndrome 2 2015-01-16 criteria provided, single submitter clinical testing
GeneDx RCV000334756 SCV000329925 pathogenic not provided 2016-08-12 criteria provided, single submitter clinical testing The Y174C pathogenic variant in the ORC4 gene has been reported previously in association with autosomal recessive Meier-Gorlin syndrome when present in the homozygous state or when in trans with another disease-causing variant (Bicknell et al., 2011; Guernsey et al., 2011). Functional studies in yeast have shown that the Y174C variant resulted in a reduced rate of growth (Guernsey et al., 2011). In addition, Y174C was reported as pathogenic in ClinVar by a different clinical laboratory, though additional evidence is not available (ClinVar SCV000248410.1; Landrum et al., 2015). The Y174C 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 Y174C variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y174C as a pathogenic variant.
SIB Swiss Institute of Bioinformatics RCV000023230 SCV000803593 likely pathogenic Meier-Gorlin syndrome 2 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Meier-Gorlin syndrome 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1-Moderate => PP1 upgraded in strength to Moderate (PMID:21358632,21358631). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:21358632,21358631).
OMIM RCV000023230 SCV000044521 pathogenic Meier-Gorlin syndrome 2 2011-02-27 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.