Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000627412 | SCV000748407 | pathogenic | not provided | 2023-12-09 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 12923596, 27905021, 11841556, 26229701, 36262015, 31980526) |
| Labcorp Genetics |
RCV003762844 | SCV002216167 | pathogenic | Ichthyosis linearis circumflexa | 2023-07-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Lys823Argfs*101) in the SPINK5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPINK5 are known to be pathogenic (PMID: 11511292, 11841556). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Netherton syndrome (PMID: 11841556, 12923596, 26229701). ClinVar contains an entry for this variant (Variation ID: 523932). |
| Juno Genomics, |
RCV000991162 | SCV005417590 | pathogenic | Netherton syndrome | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PM3_Strong+PP4 | |
| Reproductive Health Research and Development, |
RCV000991162 | SCV001142348 | pathogenic | Netherton syndrome | 2020-01-06 | no assertion criteria provided | curation | NM_006846.3:c.2468delA in the SPINK5 gene has an allele frequency of 0.005 in South subpopulation in the gnomAD database. This variant has been reported previously in individuals with Netherton syndrome, including one compound heterozygote 1608-1G>A/2468delA and one homozygote (PMID: 11841556). The c.2468delA variant causes a frameshift starting with codon Lysine 823, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 101 of the new reading frame, denoted p.Lys823Argfs*101. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Taken together, we interprete this variant as Pathogenic/Likely pathogenic variant. ACMG/AMP Criteria applied: PVS1; PM3; PP4. |