Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002317573 | SCV000851095 | uncertain significance | Inborn genetic diseases | 2016-06-30 | criteria provided, single submitter | clinical testing | The c.7702+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 55 in the SZT2 gene. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.01% (1/12970) total alleles studied and 0.01% (1/8572) European American alleles. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000802939 | SCV000942790 | uncertain significance | not provided | 2023-06-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SZT2-related conditions. This variant is present in population databases (rs374303767, gnomAD 0.009%). This sequence change falls in intron 55 of the SZT2 gene. It does not directly change the encoded amino acid sequence of the SZT2 protein. It affects a nucleotide within the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 589863). 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. 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 may create or strengthen a splice site. |
Gene |
RCV000802939 | SCV001820089 | uncertain significance | not provided | 2023-02-03 | criteria provided, single submitter | clinical testing | Identified in the heterozygous state in a patient with epilepsy in the published literature (Li et al., 2022); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 35478072) |
Genome- |
RCV003446397 | SCV004172326 | uncertain significance | Developmental and epileptic encephalopathy, 18 | 2023-04-11 | criteria provided, single submitter | clinical testing |