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.327-2A>T

CA386958679

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0f7c08ee-d25d-4a57-9136-3fd921fb08f4

HGVS expressions

NM_001306179.2:c.327-2A>T

NC_000012.12:g.120988831A>T

CM000674.2:g.120988831A>T

NC_000012.11:g.121426634A>T

CM000674.1:g.121426634A>T

NC_000012.10:g.119911017A>T

NG_011731.2:g.15086A>T

ENST00000257555.11:c.327-2A>T

ENST00000257555.10:c.327-2A>T

ENST00000400024.6:c.327-2A>T

ENST00000402929.5:n.462-2A>T

ENST00000535955.5:n.43-8660A>T

ENST00000538626.2:n.191-8660A>T

ENST00000538646.5:c.327-2A>T

ENST00000540108.1:c.327-4689A>T

ENST00000541395.5:c.327-2A>T

ENST00000541924.5:c.327-2A>T

ENST00000543427.5:c.327-2A>T

ENST00000544413.2:c.327-2A>T

ENST00000544574.5:c.73-7786A>T

ENST00000560968.5:n.470-2A>T

ENST00000615446.4:c.-257-7431A>T

ENST00000617366.4:c.327-2A>T

NM_000545.5:c.327-2A>T

NM_000545.6:c.327-2A>T

NM_001306179.1:c.327-2A>T

NM_000545.8:c.327-2A>T

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PVS1 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.327-2A>T variant in the HNF1 homeobox A gene, HNF1A, is predicted to remove a canonical splice acceptor site in intron 1 of NM_000545.8. This variant is predicted to cause skipping of biologically-relevant exon 2 of 10, resulting in a frameshift, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.327-2A>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 1.1, approved 9/30/21): PVS1, PM2_Supporting.

PVS1

Predicted to cause skipping of biologically-relevant exon 2 of 10, resulting in a frameshift, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PMID: 23348805).

PM2_Supporting

Absent from gnomAD.

Approved on: 2022-04-18

Published on: 2022-04-18

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