Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002302410 | SCV002593076 | uncertain significance | Holoprosencephaly 5 | 2022-12-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ZIC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1722291). This variant has not been reported in the literature in individuals affected with ZIC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 318 of the ZIC2 protein (p.Tyr318Cys). |
Prevention |
RCV003418445 | SCV004114351 | likely pathogenic | ZIC2-related disorder | 2022-09-23 | criteria provided, single submitter | clinical testing | The ZIC2 c.953A>G variant is predicted to result in the amino acid substitution p.Tyr318Cys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. However, this variant in located within a zinc-finger motif, where a majority of missense variants (81%, 17/21) have been detected (Fig.1, Roessler et al. 2009. PubMed ID: 19177455). This variant has also been confirmed de novo in an individual undergoing clinical exome testing (Internal Data, PreventionGenetics, LCC). This variant is interpreted as likely pathogenic. |