Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001157373 | SCV001318941 | uncertain significance | Netherton syndrome | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Neuberg Centre For Genomic Medicine, |
RCV001157373 | SCV005073895 | uncertain significance | Netherton syndrome | criteria provided, single submitter | clinical testing | The observed missense c.1739C>G(p.Pro580Arg) variant in SPINK5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with an allele frequency of 0.003% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain significance. The amino acid change p.Pro580Arg in SPINK5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Pro at position 580 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). | |
| Prevention |
RCV004758145 | SCV005362978 | uncertain significance | SPINK5-related disorder | 2024-03-08 | no assertion criteria provided | clinical testing | The SPINK5 c.1739C>G variant is predicted to result in the amino acid substitution p.Pro580Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |