Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002250356 | SCV002520644 | likely pathogenic | Monogenic diabetes | 2022-04-20 | reviewed by expert panel | curation | The c.518_526+37del variant in the HNF1 homeobox A gene, HNF1A, is a 46 base pair deletion that removes a canonical splice donor site in intron 2 of NM_000545.8. This variant is predicted to cause skipping of biologically-relevant exon 2 of 10, resulting in a frameshift, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.518_526+37del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (Specification version For HNF1A: version 1.1, Approved 9/30/21): PVS1, PM2_Supporting. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000030504 | SCV000053175 | likely pathogenic | Maturity-onset diabetes of the young type 3 | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Clinical Genomics, |
RCV002319432 | SCV002604971 | likely risk allele | 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 rs386134267 with MODY3. |