Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002250364 | SCV002520662 | uncertain significance | Monogenic diabetes | 2022-05-04 | reviewed by expert panel | curation | The c.1768+11C>T variant in the HNF1 homeobox A gene, HNF1A, is a single nucleotide variant within intron 9 of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Additionally, the computational splicing predictor SpliceAI gives a score of 0.0 for donor loss, suggesting that the variant has no impact on splicing (BP4). In summary, c.1768+11C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM2_Supporting, BP4. |
Illumina Laboratory Services, |
RCV000381111 | SCV000376724 | uncertain significance | Maturity-onset diabetes of the young type 3 | 2018-01-13 | 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. |
Clinical Genomics, |
RCV002328812 | SCV002601626 | benign | Maturity onset diabetes mellitus in young | criteria provided, single submitter | research | Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs886049034 with MODY3. |