Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV001027768 | SCV001190372 | uncertain significance | Weill-Marchesani 4 syndrome, recessive | 2021-03-30 | criteria provided, single submitter | clinical testing | ADAMTS17 NM_139057.3 exon 21 p.Ser1015Leu (c.3044C>T): This variant has not been reported in the literature but is present in 0.01% (119/75650) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/15-100516333-G-A?dataset=gnomad_r2_1). This variant amino acid Leucine (Leu) is present in >15 species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Illumina Laboratory Services, |
RCV001027768 | SCV001273668 | likely benign | Weill-Marchesani 4 syndrome, recessive | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Labcorp Genetics |
RCV001572916 | SCV002289494 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1015 of the ADAMTS17 protein (p.Ser1015Leu). This variant is present in population databases (rs143891379, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ADAMTS17-related conditions. ClinVar contains an entry for this variant (Variation ID: 827967). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Revvity Omics, |
RCV001027768 | SCV003824968 | uncertain significance | Weill-Marchesani 4 syndrome, recessive | 2021-11-29 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001572916 | SCV004131001 | likely benign | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | ADAMTS17: BP4 |
Laboratory of Diagnostic Genome Analysis, |
RCV001572916 | SCV001798011 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001572916 | SCV001969637 | likely benign | not provided | no assertion criteria provided | clinical testing |