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.1768G>A (p.Val590Met)

CA386973441

447484 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3fa64ca7-d2ab-4397-85da-22418f47c681

Approved on: 2022-04-17

Published on: 2022-04-17

HGVS expressions

NM_000545.8:c.1768G>A

NM_000545.8(HNF1A):c.1768G>A (p.Val590Met)

NC_000012.12:g.120999627G>A

CM000674.2:g.120999627G>A

NC_000012.11:g.121437430G>A

CM000674.1:g.121437430G>A

NC_000012.10:g.119921813G>A

NG_011731.2:g.25882G>A

ENST00000257555.11:c.1768G>A

ENST00000257555.10:c.1768G>A

ENST00000540108.1:c.*1208G>A

ENST00000541395.5:c.1861G>A

ENST00000543427.5:c.1231G>A

ENST00000544413.2:c.1789G>A

ENST00000560968.5:n.1585G>A

ENST00000615446.4:c.556G>A

ENST00000617366.4:c.*177G>A

NM_000545.5:c.1768G>A

NM_000545.6:c.1768G>A

NM_001306179.1:c.1789G>A

NM_001306179.2:c.1789G>A

Uncertain Significance

PM2_Supporting

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1768C>G variant in the e.g. HNF1 homeobox A gene, HNF1A, causes an amino acid change of valine to methionine at codon 590(p.(Arg583Gly)) of NM_000545.8. This variant has a minor allele frequency of 0.000009 in the gnomAD v2.1.1 European non-Finnish population and no copies in another subpopulation, which is less than the ClinGen MDEP threshold for PM2_Supporting (≤0.00002 and ≤1 copy in any other subpopulation) (PM2_Supporting). In summary, c.1768C>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 1.1, approved 9/30/21): PM2_Supporting.

PM2_Supporting

0.000009 < 0.00002 in gnomAD 2.1.1 ENF, no copies in other subpopulations

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