Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV005054209 | SCV005687813 | uncertain significance | Monogenic diabetes | 2025-01-29 | reviewed by expert panel | curation | The c.670+7C>T variant in the HNF4 homeobox A gene, HNF4A, is a single nucleotide variant within intron 6 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 has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.00002141 which is lower than the MDEP threshold for BS1 (0.000033) and greater than the MDEP threshold for PM2 (0.000003). This variant was identified in an individual with a clinical history highly specific for HNF4A-MODY (MODY probability calculator result >50% and negative genetic testing for HNF1A) (PP4; internal lab contributor).In summary, c.670+7C>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 2.0.0, approved 10/11/2023): BP4, PP4. |
| Labcorp Genetics |
RCV005091185 | SCV005731286 | likely benign | not provided | 2024-09-29 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005027601 | SCV005656981 | likely benign | Maturity-onset diabetes of the young type 1; Type 2 diabetes mellitus; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young | 2024-05-24 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV003148767 | SCV003804765 | benign | Maturity-onset diabetes of the 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 rs376544046 in MODY, yet. | |
| Athena Diagnostics | RCV000518627 | SCV000613658 | likely benign | not specified | 2017-06-05 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003905300 | SCV004722658 | likely benign | HNF4A-related disorder | 2019-03-04 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |