Variant: NM_001306179.2:c.42_51delinsTG

CA2573051031

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: 434b8bdf-85ee-4f12-ac91-a025d44a6eb2

HGVS expressions

NM_001306179.2:c.42_51delinsTG
NC_000012.12:g.120978810_120978819delinsTG
CM000674.2:g.120978810_120978819delinsTG
NC_000012.11:g.121416613_121416622delinsTG
CM000674.1:g.121416613_121416622delinsTG
NC_000012.10:g.119900996_119901005delinsTG
NG_011731.2:g.5065_5074delinsTG
ENST00000257555.11:c.42_51delinsTG
ENST00000257555.10:c.42_51delinsTG
ENST00000400024.6:c.42_51delinsTG
ENST00000402929.5:n.177_186delinsTG
ENST00000535955.5:n.42+118_42+127delinsTG
ENST00000538626.2:n.160_169delinsTG
ENST00000538646.5:c.42_51delinsTG
ENST00000540108.1:c.42_51delinsTG
ENST00000541395.5:c.42_51delinsTG
ENST00000541924.5:c.42_51delinsTG
ENST00000543427.5:c.42_51delinsTG
ENST00000544413.2:c.42_51delinsTG
ENST00000544574.5:c.42_51delinsTG
ENST00000560968.5:n.185_194delinsTG
ENST00000615446.4:c.-258+99_-258+108delinsTG
ENST00000617366.4:c.42_51delinsTG
NM_000545.5:c.42_51delinsTG
NM_000545.6:c.42_51delinsTG
NM_001306179.1:c.42_51delinsTG
NM_000545.8:c.42_51delinsTG

Pathogenic

• Met criteria codes: PM2_Supporting PP4_Moderate PVS1

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

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.42_51delGGCCCTGCTCinsTG variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 15 (NM_000545.8), adding 15 novel amino acids before encountering a stop codon (p.(Ala15GlyfsTer15)). 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). This variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and antibody negative) (PP4_Moderate; internal lab contributor). In summary, c.42_51delGGCCCTGCTCinsTG meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.0, approved 9/30/21): PVS1, PM2_Supporting, PP4_Moderate.

Met criteria codes

• PM2_Supporting: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4_Moderate: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2022-03-31

Published on: 2022-07-12