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]

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Variant: NM_000545.8(HNF1A):c.73G>A (p.Ala25Thr)

CA160004

134506 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 62eed938-2e39-4d07-bfed-84ae2b97533d

Approved on: 2022-04-01

Published on: 2022-07-12

HGVS expressions

NM_000545.8:c.73G>A

NM_000545.8(HNF1A):c.73G>A (p.Ala25Thr)

NC_000012.12:g.120978841G>A

CM000674.2:g.120978841G>A

NC_000012.11:g.121416644G>A

CM000674.1:g.121416644G>A

NC_000012.10:g.119901027G>A

NG_011731.2:g.5096G>A

ENST00000257555.11:c.73G>A

ENST00000257555.10:c.73G>A

ENST00000400024.6:c.73G>A

ENST00000402929.5:n.208G>A

ENST00000535955.5:n.42+149G>A

ENST00000538626.2:n.190+1G>A

ENST00000538646.5:c.73G>A

ENST00000540108.1:c.73G>A

ENST00000541395.5:c.73G>A

ENST00000541924.5:c.73G>A

ENST00000543427.5:c.73G>A

ENST00000544413.2:c.73G>A

ENST00000544574.5:c.72+1G>A

ENST00000560968.5:n.216G>A

ENST00000615446.4:c.-258+130G>A

ENST00000617366.4:c.73G>A

NM_000545.5:c.73G>A

NM_000545.6:c.73G>A

NM_001306179.1:c.73G>A

NM_001306179.2:c.73G>A

Uncertain Significance

PM1_Supporting PM2_Supporting

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 Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.73G>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of Alanine to Threonine at codon 25 (p.(Ala25Thr)) of transcript NM_000545.8. This variant is located within the dimerization domain (codons 1-32) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.73G>A meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1_supporting, PM2_supporting.

PM1_Supporting

This variant occurs within the dimerization domain of HNF1A.

PM2_Supporting

This variant is absent from gnomAD.

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