ClinVar Miner

Submissions for variant NM_181742.3(ORC4):c.521A>G (p.Tyr174Cys) (rs387906847)

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Total submissions: 4
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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

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