Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002468459 | SCV002764329 | uncertain significance | Maturity-onset diabetes of the young type 1; Type 2 diabetes mellitus | 2022-07-01 | criteria provided, single submitter | clinical testing | The c.709A>G p.(Met237Val) variant identified in the HNF4A gene substitutes a well conserved Methionine for Valine at amino acid 237/475 (exon 6/10). This variant is found with low frequency in gnomADv2.1.1 (2 heterozygotes, 0 homozygotes; allele frequency:7.978e-6) and is absent from gnomADv3.1.2, BRAVO-TOPMed Freeze 8, and All of Us datasets, suggesting it is not a common benign variant in the populations represented in those databases. In silico algorithms predict this variant to be Pathogenic (REVEL=0.805) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity, the c.709A>Gp.(Met237Val) variant identified in the HNF4A gene is reported as a Variant of Uncertain Significance. |