Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002996240 | SCV003300943 | uncertain significance | Holoprosencephaly 5 | 2022-05-24 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ZIC2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 481 of the ZIC2 protein (p.Gly481Val). |
Ambry Genetics | RCV004068475 | SCV004983960 | uncertain significance | Inborn genetic diseases | 2023-12-20 | criteria provided, single submitter | clinical testing | The c.1442G>T (p.G481V) alteration is located in exon 3 (coding exon 3) of the ZIC2 gene. This alteration results from a G to T substitution at nucleotide position 1442, causing the glycine (G) at amino acid position 481 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |