Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000350822 | SCV000384698 | uncertain significance | ALG11-congenital disorder of glycosylation | 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. |
| Gene |
RCV000493317 | SCV000581742 | uncertain significance | not provided | 2018-10-12 | criteria provided, single submitter | clinical testing | The c.44G>C variant in the ALG11 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.44G>C variant is observed in 1/6,494 (0.02%) alleles from individuals of European (Finnish) background, and in 3/66,152 (.005%) alleles from individuals of European (non-Finnish) background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). In-silico splice prediction models predict that c.44G>C may cause loss of the natural splice donor site in intron 1. However, in the absence of RNA/functional studies, the actual effect of the c.44G>C change in this individual is unknown. If c.44G>C does not alter splicing, it will result in the R15T missense change. The R15T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.44G>C as a variant of uncertain significance. |