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

CA386965322

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 01f144b9-fcad-4bcd-a327-809f636f1bf5

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001306179.2:c.700G>T

NC_000012.12:g.120993693G>T

CM000674.2:g.120993693G>T

NC_000012.11:g.121431496G>T

CM000674.1:g.121431496G>T

NC_000012.10:g.119915879G>T

NG_011731.2:g.19948G>T

ENST00000560968.6:c.700G>T

ENST00000257555.11:c.700G>T

ENST00000257555.10:c.700G>T

ENST00000400024.6:c.700G>T

ENST00000402929.5:n.835G>T

ENST00000535955.5:n.43-3798G>T

ENST00000538626.2:n.191-3798G>T

ENST00000538646.5:c.527-471G>T

ENST00000540108.1:c.*140G>T

ENST00000541395.5:c.700G>T

ENST00000541924.5:c.700G>T

ENST00000543427.5:c.633+67G>T

ENST00000544413.2:c.700G>T

ENST00000544574.5:c.73-2924G>T

ENST00000560968.5:c.843G>T

ENST00000615446.4:c.-257-2569G>T

ENST00000617366.4:c.586+114G>T

NM_000545.5:c.700G>T

NM_000545.6:c.700G>T

NM_001306179.1:c.700G>T

NM_000545.8:c.700G>T

Likely Pathogenic

PM2_Supporting PVS1

PS4 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.700G>T variant in the HNF1 homeobox A gene, HNF1A, results in a premature termination at codon 234 (p.(Glu234Ter)) of NM_000545.8. This variant, located in biologically-relevant exon 3 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information (PMID: 15928245). In summary, c.700G>T meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/2023): PVS1, PM2_Supporting.

PM2_Supporting

This variant is absent in gnomAD v2.1.1 (PM2_Supporting).

PVS1

This variant, located in biologically-relevant exon 3 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID:23348805).

PS4

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 MODY probability is unable to be calculated due to lack of clinical information (PMID:15928245).

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