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.811del

CA915940438

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9331c89b-5ffd-4911-b3d0-fe77a2b17f41

HGVS expressions

NM_001306179.2:c.811del

NC_000012.12:g.120994261del

CM000674.2:g.120994261del

NC_000012.11:g.121432064del

CM000674.1:g.121432064del

NC_000012.10:g.119916447del

NG_011731.2:g.20516del

ENST00000257555.11:c.811del

ENST00000257555.10:c.811del

ENST00000400024.6:c.811del

ENST00000402929.5:n.946del

ENST00000535955.5:n.43-3230del

ENST00000538626.2:n.191-3230del

ENST00000538646.5:c.624del

ENST00000540108.1:c.*251del

ENST00000541395.5:c.811del

ENST00000541924.5:c.713+555del

ENST00000543427.5:c.633+635del

ENST00000544413.2:c.811del

ENST00000544574.5:c.73-2356del

ENST00000560968.5:n.893+61del

ENST00000615446.4:c.-257-2001del

ENST00000617366.4:c.586+682del

NM_000545.5:c.811del

NM_000545.6:c.811del

NM_001306179.1:c.811del

NM_000545.8:c.811del

Likely Pathogenic

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

PVS1_Strong PM2_Supporting

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 Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.811del variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 271 NM_000545.8, adding 71 novel amino acids before encountering a stop codon (p.(Arg271GlyfsTer71). 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 absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested, and PP4 will not be applied (PMID: 16917892, internal lab contributors). In summary, c.811delC 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_Strong

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.

PP4

This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (PMID: 16917892, internal lab contributors).

Approved on: 2022-04-13

Published on: 2022-07-12

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