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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001306179.2:c.332A>G

CA386958785

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5528da7b-db18-4bf8-929a-93984c89e4e4

HGVS expressions

NM_001306179.2:c.332A>G

NC_000012.12:g.120988838A>G

CM000674.2:g.120988838A>G

NC_000012.11:g.121426641A>G

CM000674.1:g.121426641A>G

NC_000012.10:g.119911024A>G

NG_011731.2:g.15093A>G

ENST00000257555.11:c.332A>G

ENST00000257555.10:c.332A>G

ENST00000400024.6:c.332A>G

ENST00000402929.5:n.467A>G

ENST00000535955.5:n.43-8653A>G

ENST00000538626.2:n.191-8653A>G

ENST00000538646.5:c.332A>G

ENST00000540108.1:c.327-4682A>G

ENST00000541395.5:c.332A>G

ENST00000541924.5:c.332A>G

ENST00000543427.5:c.332A>G

ENST00000544413.2:c.332A>G

ENST00000544574.5:c.73-7779A>G

ENST00000560968.5:c.475A>G

ENST00000615446.4:c.-257-7424A>G

ENST00000617366.4:c.332A>G

NM_000545.5:c.332A>G

NM_000545.6:c.332A>G

NM_001306179.1:c.332A>G

NM_000545.8:c.332A>G

Uncertain Significance

PM1_Supporting PP3 PM2_Supporting

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.332A>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of aspartic acid to glycine at codon 111 (p.(Asp111Gly)) of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.985, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual(s) with diabetes; however, the calculated MODY probability is <50% and HNF4A was not tested (internal lab contributors). In summary, c.332A>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): PP3, PM_Supporting, PM2_Supporting.

PM1_Supporting

This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting).

PP3

This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.985, which is greater than the MDEP VCEP threshold of 0.70 (PP3).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Absent from gnomAD v4.0

PP4

This variant was identified in an individual(s) with diabetes; however, the calculated MODY probability is <50% and HNF4A was not tested (internal lab contributors).

Approved on: 2024-01-28

Published on: 2024-01-28

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