Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004599222 | SCV000673544 | uncertain significance | not specified | 2024-03-16 | criteria provided, single submitter | clinical testing | The p.W2L variant (also known as c.5G>T), located in coding exon 1 of the GALNT12 gene, results from a G to T substitution at nucleotide position 5. The tryptophan at codon 2 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV000821211 | SCV000961960 | uncertain significance | not provided | 2024-08-06 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 2 of the GALNT12 protein (p.Trp2Leu). 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 variant has not been reported in the literature in individuals affected with GALNT12-related conditions. ClinVar contains an entry for this variant (Variation ID: 485653). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "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. |
| Baylor Genetics | RCV004569270 | SCV005058791 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000821211 | SCV005623161 | uncertain significance | not provided | 2024-02-09 | criteria provided, single submitter | clinical testing | The GALNT12 c.5G>T (p.Trp2Leu) variant has not been reported in individuals with GALNT12-related conditions in the published literature. The frequency of this variant in the general population, 0.000055 (2/36452 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Fulgent Genetics, |
RCV004569270 | SCV005677623 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2024-04-24 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004752951 | SCV005366807 | uncertain significance | GALNT12-related disorder | 2024-04-08 | no assertion criteria provided | clinical testing | The GALNT12 c.5G>T variant is predicted to result in the amino acid substitution p.Trp2Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of African descent in gnomAD and is interpreted as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/485653/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |