Variant: NM_000545.8(HNF1A):c.-258A>G

CA244520152

1342947 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: efb4d64f-a41f-4a05-9ecc-f176c6970bfe

Approved on: 2024-01-18

Published on: 2024-01-18

HGVS expressions

NM_000545.8:c.-258A>G
NM_000545.8(HNF1A):c.-258A>G
NC_000012.12:g.120978511A>G
CM000674.2:g.120978511A>G
NC_000012.11:g.121416314A>G
CM000674.1:g.121416314A>G
NC_000012.10:g.119900697A>G
NG_011731.2:g.4766A>G

Uncertain Significance

• Met criteria codes: PM1_Supporting PP4

• Not Met criteria codes: PM2 PS4 PP1

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.-258A>G variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This variant is located in the promoter of NM_000545.8. This variant is located at the HNF1A binding site (c.-238 to c.-259) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). Additionally, this variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A) (PP4; internal lab contributor). In summary, c.-258A>G 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 2.1.0, approved 8/11/2023): PM1_Supporting, PP4.

Met criteria codes

• PM1_Supporting: This variant is located in the promoter of NM_000545.8. This variant is located at the HNF1A binding site (c.-238 to c.-259) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP.
• PP4: This variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A).

Not Met criteria codes

• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline