Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001948085 | SCV002196952 | uncertain significance | Netherton syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 19 of the SPINK5 gene. It does not directly change the encoded amino acid sequence of the SPINK5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Netherton syndrome (PMID: 22089833). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 22089833). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526882 | SCV005039866 | uncertain significance | not specified | 2024-03-18 | criteria provided, single submitter | clinical testing | Variant summary: SPINK5 c.1820+53G>A is located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. At least one publication reports experimental evidence that this variant affects mRNA splicing and leads to a leaky variant that is not sufficient to prevent disease (Lacroix_2012). The variant was absent in 249032 control chromosomes (gnomAD). c.1820+53G>A has been reported in the literature in at-least one individual affected with Netherton syndrome (Lacroix_2012). The following publication has been ascertained in the context of this evaluation (PMID: 22089833). ClinVar contains an entry for this variant (Variation ID: 1417211). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |