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_000545.8(HNF1A):c.1623+3A>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10587145

256598 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4d08e15d-7c27-4174-9937-728646b86912

Approved on: 2022-05-03

Published on: 2022-05-03

HGVS expressions

NM_000545.8:c.1623+3A>G

NM_000545.8(HNF1A):c.1623+3A>G

NC_000012.12:g.120999392A>G

CM000674.2:g.120999392A>G

NC_000012.11:g.121437195A>G

CM000674.1:g.121437195A>G

NC_000012.10:g.119921578A>G

NG_011731.2:g.25647A>G

ENST00000257555.11:c.1623+3A>G

ENST00000257555.10:c.1623+3A>G

ENST00000540108.1:c.*1063+3A>G

ENST00000541395.5:c.1626A>G

ENST00000543427.5:c.1086+3A>G

ENST00000544413.2:c.1623+3A>G

ENST00000560968.5:n.1440+3A>G

ENST00000615446.4:c.411+3A>G

ENST00000617366.4:c.*32+3A>G

NM_000545.5:c.1623+3A>G

NM_000545.6:c.1623+3A>G

NM_001306179.1:c.1623+3A>G

NM_001306179.2:c.1623+3A>G

Uncertain Significance

BP4 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.1623+3A>G variant in the HNF1 homeobox A gene, HNF1A, is predicted to remove a canonical splice donor site in intron 8 of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.0 for donor loss, suggesting that the variant has no impact on splicing (BP4). In summary, c.1623+3A>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 9/30/2021): PM2_Supporting, BP4.

BP4

The computational splicing predictor SpliceAI gives a score of 0.00 for donor/acceptor loss, suggesting that the variant has no impact on splicing.

PM2_Supporting

Absent from gnomAD.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.