Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000579317 | SCV000681388 | uncertain significance | not provided | 2023-09-28 | criteria provided, single submitter | clinical testing | Identified in a cohort of individuals with cardiovascular disease, but no additional clinical information was provided (Glicksberg et al., 2019); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31345219) |
Mayo Clinic Laboratories, |
RCV000660438 | SCV000782528 | likely pathogenic | ALG8 congenital disorder of glycosylation | 2016-11-16 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000660438 | SCV000915559 | uncertain significance | ALG8 congenital disorder of glycosylation | 2017-04-28 | criteria provided, single submitter | clinical testing | The ALG8 c.478+1G>A variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL 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 for this variant, it 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 and cDNA change. No publications were found based on this search. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital disorders of glycosylation. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Baylor Genetics | RCV000660438 | SCV001526951 | likely pathogenic | ALG8 congenital disorder of glycosylation | criteria provided, single submitter | clinical testing | ||
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000579317 | SCV002061430 | uncertain significance | not provided | 2021-07-23 | criteria provided, single submitter | clinical testing | PVS1 |
Invitae | RCV000660438 | SCV003253821 | likely pathogenic | ALG8 congenital disorder of glycosylation | 2022-04-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the ALG8 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ALG8 are known to be pathogenic (PMID: 19862844). This variant is present in population databases (rs139832787, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ALG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 489384). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Revvity Omics, |
RCV000579317 | SCV003830873 | likely pathogenic | not provided | 2022-04-18 | criteria provided, single submitter | clinical testing |