Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003228641 | SCV003925324 | uncertain significance | Type 2 diabetes mellitus | 2022-09-21 | criteria provided, single submitter | clinical testing | The c.11A>G variant in HNF1B has not previously been reported in the literature or public variant repositories (ClinVar and LOVD). The c.11A>G variant is observed in 3alleles (0.0005% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), suggesting it is not a common benign variant in the populations represented in those databases. The c.11A>G variant in HNF1B is located in exon 1 of this 9-exon gene and is predicted to replace a moderately conserved lysine with arginine at position 4 in the dimerization domain [PMID: 33434175] of the encoded protein. In silico predictions are inconclusive of the variant's p. (Lys4Arg) effect [(CADD v1.6 = 24.3, REVEL = 0.498)]; however, there are no functional studies to support or refute these predictions. Based on available evidence, this c.11A>G, p.(Lys4Arg) variant identified in HNF1B is classified as a Variant of Uncertain Significance. |