Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003595661 | SCV001199958 | likely pathogenic | Ichthyosis linearis circumflexa | 2023-03-17 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 835648). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in activation of a cryptic splice donor site and introduces a premature termination codon (PMID: 11841556). The resulting mRNA is expected to undergo nonsense-mediated decay. This variant has been observed in individual(s) with Netherton syndrome (PMID: 11841556). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs771730802, gnomAD 0.002%). This sequence change falls in intron 2 of the SPINK5 gene. It does not directly change the encoded amino acid sequence of the SPINK5 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |