Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002050620 | SCV002116808 | uncertain significance | Pigmentary pallidal degeneration | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 255 of the PANK2 protein (p.Asn255Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs143474105, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with PANK2-related conditions. 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: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV002543491 | SCV003699571 | uncertain significance | Inborn genetic diseases | 2022-08-17 | criteria provided, single submitter | clinical testing | The c.764A>G (p.N255S) alteration is located in exon 2 (coding exon 2) of the PANK2 gene. This alteration results from a A to G substitution at nucleotide position 764, causing the asparagine (N) at amino acid position 255 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |