Variant: NM_001306179.2:c.71_72del

CA2573051032

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: 7c657597-6696-40fe-b86a-fdfdd4f238e3

HGVS expressions

NM_001306179.2:c.71_72del
NC_000012.12:g.120978839_120978840del
CM000674.2:g.120978839_120978840del
NC_000012.11:g.121416642_121416643del
CM000674.1:g.121416642_121416643del
NC_000012.10:g.119901025_119901026del
NG_011731.2:g.5094_5095del
ENST00000257555.11:c.71_72del
ENST00000257555.10:c.71_72del
ENST00000400024.6:c.71_72del
ENST00000402929.5:n.206_207del
ENST00000535955.5:n.42+147_42+148del
ENST00000538626.2:n.189_190del
ENST00000538646.5:c.71_72del
ENST00000540108.1:c.71_72del
ENST00000541395.5:c.71_72del
ENST00000541924.5:c.71_72del
ENST00000543427.5:c.71_72del
ENST00000544413.2:c.71_72del
ENST00000544574.5:c.71_72del
ENST00000560968.5:n.214_215del
ENST00000615446.4:c.-258+128_-258+129del
ENST00000617366.4:c.71_72del
NM_000545.5:c.71_72del
NM_000545.6:c.71_72del
NM_001306179.1:c.71_72del
NM_000545.8:c.71_72del

Pathogenic

• Met criteria codes: PP1 PVS1 PM2_Supporting

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.71_72delAG variant in the HNF1 homeobox A gene, HNF1A, is a two base pair deletion resulting in a frameshift in the protein at codon 24 in NM_000545.8, adding 8 novel amino acids before encountering a stop codon (p.(Glu24GlyfsTer8)). 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 segregated with diabetes, with three informative meioses in one family (PP1; PMID: 12453976). In summary, this variant meets the criteria to be classified as 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, PP1.

Met criteria codes

• PP1: This variant segregated with diabetes, with three informative meioses in one family (PP1; PMID: 12453976)
• PVS1: 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 (PMID: 23348805).
• PM2_Supporting: This variant is absent from gnomAD v2.1.1.

Approved on: 2022-04-01

Published on: 2022-07-12