Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001038444 | SCV001201911 | uncertain significance | Early myoclonic encephalopathy | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the KCND2 gene. It does not directly change the encoded amino acid sequence of the KCND2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368783057, gnomAD 0.06%), 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 KCND2-related conditions. ClinVar contains an entry for this variant (Variation ID: 837167). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
Center for Genomics, |
RCV002067718 | SCV002495814 | uncertain significance | not provided | 2021-03-30 | criteria provided, single submitter | clinical testing | KCND2 NM_012281.2 intron 2 c.1278+4C>T: This variant has not been reported in the literature but is present in 0.05% (40/68026) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/7-120733069-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:837167). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant occurs in the splice region, computational prediction tools do not suggest that it alters splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Ambry Genetics | RCV004986739 | SCV005598404 | likely benign | Inborn genetic diseases | 2024-07-08 | 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. |