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.313dup (p.Glu105fs)

CA214298

36817 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cc3f16f5-5674-402d-a312-71bc457dbb8a

HGVS expressions

NM_000545.8:c.313dup

NM_000545.8(HNF1A):c.313dup (p.Glu105fs)

NC_000012.12:g.120979081dup

CM000674.2:g.120979081dup

NC_000012.11:g.121416884dup

CM000674.1:g.121416884dup

NC_000012.10:g.119901267dup

NG_011731.2:g.5336dup

ENST00000257555.11:c.313dup

ENST00000257555.10:c.313dup

ENST00000400024.6:c.313dup

ENST00000402929.5:n.448dup

ENST00000535955.5:n.42+389dup

ENST00000538626.2:n.190+241dup

ENST00000538646.5:c.313dup

ENST00000540108.1:c.313dup

ENST00000541395.5:c.313dup

ENST00000541924.5:c.313dup

ENST00000543427.5:c.313dup

ENST00000544413.2:c.313dup

ENST00000544574.5:c.72+241dup

ENST00000560968.5:n.456dup

ENST00000615446.4:c.-258+370dup

ENST00000617366.4:c.313dup

NM_000545.5:c.313dup

NM_000545.6:c.313dup

NM_001306179.1:c.313dup

NM_001306179.2:c.313dup

Likely Pathogenic

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

PM2_Supporting PVS1_Strong

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 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.313dupG variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 105 (NM_000545.8), adding 83 novel amino acids before encountering a stop codon (p.(Glu105GlyfsTer83)). This variant, located in biologically-relevant exon 1 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). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.313dupG 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.

PM2_Supporting

This variant is absent from gnomAD.

PVS1_Strong

A transcript with this variant is predicted to undergo nonsense mediated decay and this exon is present in a biologically relevant transcript.

Approved on: 2022-04-07

Published on: 2022-07-12

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.