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_000545.8(HNF1A):c.326+2T>G

CA386955008

447486 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d84441f5-1ea5-427b-8f5a-702c0381aea8

HGVS expressions

NM_000545.8:c.326+2T>G

NM_000545.8(HNF1A):c.326+2T>G

NC_000012.12:g.120979096T>G

CM000674.2:g.120979096T>G

NC_000012.11:g.121416899T>G

CM000674.1:g.121416899T>G

NC_000012.10:g.119901282T>G

NG_011731.2:g.5351T>G

ENST00000257555.11:c.326+2T>G

ENST00000257555.10:c.326+2T>G

ENST00000400024.6:c.326+2T>G

ENST00000402929.5:n.461+2T>G

ENST00000535955.5:n.42+404T>G

ENST00000538626.2:n.190+256T>G

ENST00000538646.5:c.326+2T>G

ENST00000540108.1:c.326+2T>G

ENST00000541395.5:c.326+2T>G

ENST00000541924.5:c.326+2T>G

ENST00000543427.5:c.326+2T>G

ENST00000544413.2:c.326+2T>G

ENST00000544574.5:c.72+256T>G

ENST00000560968.5:n.469+2T>G

ENST00000615446.4:c.-258+385T>G

ENST00000617366.4:c.326+2T>G

NM_000545.5:c.326+2T>G

NM_000545.6:c.326+2T>G

NM_001306179.1:c.326+2T>G

NM_001306179.2:c.326+2T>G

Likely Pathogenic

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

PVS1 PM2_Supporting

PM5

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.326+2T>G variant in the HNF1 homeobox A gene, HNF1A, is predicted to remove a canonical splice donor 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.326+2T>G 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 9/30/2021): PVS1, PM2_Supporting.

PVS1

A transcript with this variant is predicted to undergo nonsense mediated decay.

PM2_Supporting

This variant is absent from gnomAD.

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-04-07

Published on: 2022-07-12

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