ClinVar Miner

Submissions for variant NM_014321.4(ORC6):c.2T>C (p.Met1Thr) (rs146795505)

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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 RCV000239616 SCV000596182 pathogenic Meier-Gorlin syndrome 3 2016-05-05 criteria provided, single submitter clinical testing
GeneDx RCV000579163 SCV000680778 pathogenic not provided 2015-12-07 criteria provided, single submitter clinical testing The c.2 T>C pathogenic variant in the ORC6 gene has been reported previously in trans with a splice site variant in four individuals with Meier-Gorlin syndrome from three families (de Munnik et al., 2012). The c.2 T>C variant alters the initiator Methionine codon, and the resultant protein would be described as p.Met1? using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. The c.2 T>C variant was not observed at any significant frequency 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. We interpret c.2 T>C as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000239616 SCV000915715 likely pathogenic Meier-Gorlin syndrome 3 2019-01-12 criteria provided, single submitter clinical testing The ORC6 c.2T>C (p.Met1?) variant is a stop-lost variant that is predicted to result in an elongation of the protein. This variant has been reported in one study and is found in a compound heterozygous state in four individuals from three families with Meier-Gorlin syndrome (De Munnik et al. 2012). The p.Met1? variant is reported at a frequency of 0.000601 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence, the p.Met1? variant is classified likely pathogenic for Meier-Gorlin syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000239616 SCV000298176 pathogenic Meier-Gorlin syndrome 3 2016-08-30 no assertion criteria provided literature only

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