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.722_725dup (p.Ile242fs)

CA658658177

452526 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2118292a-2a27-4cdf-90d1-b7b4417c94a0

HGVS expressions

NM_000545.8:c.722_725dup

NM_000545.8(HNF1A):c.722_725dup (p.Ile242fs)

NC_000012.12:g.120994172_120994175dup

CM000674.2:g.120994172_120994175dup

NC_000012.11:g.121431975_121431978dup

CM000674.1:g.121431975_121431978dup

NC_000012.10:g.119916358_119916361dup

NG_011731.2:g.20427_20430dup

ENST00000257555.11:c.722_725dup

ENST00000257555.10:c.722_725dup

ENST00000400024.6:c.722_725dup

ENST00000402929.5:n.857_860dup

ENST00000535955.5:n.43-3319_43-3316dup

ENST00000538626.2:n.191-3319_191-3316dup

ENST00000538646.5:c.535_538dup

ENST00000540108.1:c.*162_*165dup

ENST00000541395.5:c.722_725dup

ENST00000541924.5:c.713+466_713+469dup

ENST00000543427.5:c.633+546_633+549dup

ENST00000544413.2:c.722_725dup

ENST00000544574.5:c.73-2445_73-2442dup

ENST00000560968.5:n.865_868dup

ENST00000615446.4:c.-257-2090_-257-2087dup

ENST00000617366.4:c.586+593_586+596dup

NM_000545.5:c.722_725dup

NM_000545.6:c.722_725dup

NM_001306179.1:c.722_725dup

NM_001306179.2:c.722_725dup

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 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.722_725dup variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 242 of NM_000545.8, adding 76 novel amino acids before encountering a stop codon (p.Ile242MetfsTer76). This variant, located in biologically-relevant exon 4 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 also absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.722_725dup 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

This variant is predicted to cause loss of function by resulting in the nonsense mediated decay of a biologically relevant exon.

PM2_Supporting

This variant is absent from gnomAD.

Approved on: 2022-04-12

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.