Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004797827 | SCV005420260 | likely benign | Monogenic diabetes | 2024-12-02 | reviewed by expert panel | curation | The c.826+79C>T variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, is a single nucleotide variant within intron 7 of NM_175914.5 . The computational splicing predictor SpliceAI gives a score of 0.00 for donor loss, suggesting that the variant has no impact on splicing (BP4). This variant is not covered in gnomAD v2.1.1 exomes and has a Grpmax Filtering allele frequency of 0.000068 in gnomAD v3.1.2, which is greater than the MDEP threshold for BS1 (greater than or equal to 0.000033)(BS1). In summary, c.826+79C>T meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BS1, BP4. |
Athena Diagnostics | RCV000517003 | SCV000613662 | uncertain significance | not specified | 2017-07-06 | criteria provided, single submitter | clinical testing | |
Clinical Genomics, |
RCV003148768 | SCV003804775 | benign | Maturity onset diabetes mellitus in young | criteria provided, single submitter | research | Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs773386088 in MODY, yet. |