Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000530244 | SCV000655225 | uncertain significance | Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome | 2017-05-31 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on GLI2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Family studies have indicated that an individual, with clinical features consistent with GLI2-related disease, inherited this variant from an unaffected parent. This suggests that the variant is not likely a primary cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with serine at codon 514 of the GLI2 protein (p.Tyr514Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. |
| Gene |
RCV002253509 | SCV002525313 | uncertain significance | not provided | 2021-12-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |