Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002011521 | SCV002301705 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 380 of the KANK2 protein (p.Arg380Cys). This variant is present in population databases (rs144821191, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KANK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510116). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Fulgent Genetics, |
RCV002486685 | SCV002799702 | uncertain significance | Wooly hair-palmoplantar keratoderma syndrome; Nephrotic syndrome 16 | 2022-03-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004046661 | SCV004889073 | likely benign | not specified | 2022-04-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV003948870 | SCV004771077 | uncertain significance | KANK2-related disorder | 2023-12-29 | no assertion criteria provided | clinical testing | The KANK2 c.1138C>T variant is predicted to result in the amino acid substitution p.Arg380Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-11303618-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |