Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004577195 | SCV005061094 | likely pathogenic | Pseudopseudohypoparathyroidism | criteria provided, single submitter | clinical testing | The observed stop gain variant c.34C>T (p.Arg12Ter) in GNAS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.34C>T variant is absent in gnomAD Exomes database. This variant has not been submitted to the ClinVar database. The nucleotide change c.34C>T in GNAS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Mutation taster predicts that this variant is likely to undergo non-sense mediated decay. Loss of function variant in GNAS gene have been reported previously in individuals affected with pseudohypoparathyroidism Ia, pseudopseudohypoparathyroidism, and progressive osseous heteroplasia. Additional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic. |