Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001306179.2:c.-197C>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA2797727079

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f7870d58-7c8e-4591-b286-999d06651956

Approved on: 2025-02-28

Published on: 2025-02-28

HGVS expressions

NM_001306179.2:c.-197C>T

NC_000012.12:g.120978572C>T

CM000674.2:g.120978572C>T

NC_000012.11:g.121416375C>T

CM000674.1:g.121416375C>T

NC_000012.10:g.119900758C>T

NG_011731.2:g.4827C>T

ENST00000257555.11:c.-197C>T

ENST00000257555.10:c.-197C>T

ENST00000400024.6:c.-197C>T

NM_000545.6:c.-197C>T

NM_001306179.1:c.-197C>T

NM_000545.8:c.-197C>T

Uncertain Significance

PM2_Supporting

PS4 PM1 PP4

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.-197C>T variant in the HNF1 homeobox A gene, HNF1A, is a single nucleotide variant within the 5' UTR of NM_000545.8. This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). Additionally, PP4 cannot be applied as the calculated MODY probability is <50% (internal lab contributors). In summary, c.-197C>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 2.1.0, approved 08/11/2023): PM2_Supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting).

PS4

This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors).

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (internal lab contributors).

Curation History

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