NM_000545.8:c.-167TGGGGGT[3]

CA6831598

288582 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: 1ea61993-812d-49ae-b73a-947b1f25997d

HGVS expressions

NM_000545.8:c.-167TGGGGGT[3]
NC_000012.12:g.120978609_120978615dup
CM000674.2:g.120978609_120978615dup
NC_000012.11:g.121416412_121416418dup
CM000674.1:g.121416412_121416418dup
NC_000012.10:g.119900795_119900801dup
NG_011731.2:g.4864_4870dup
ENST00000257555.11:c.-160_-154dup
ENST00000257555.10:c.-160_-154dup
ENST00000400024.6:c.-160_-154dup
NM_000545.6:c.-160_-154dup
NM_001306179.1:c.-160_-154dup
NM_000545.8:c.-160_-154dup
NM_001306179.2:c.-160_-154dup
NM_000545.8(HNF1A):c.-167TGGGGGT[3]

Benign

• Met criteria codes: BA1 BP5

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.-160_-154dup variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.013, which is greater thanthe MDEP threshold for BA1 (≥0.0001) (BA1). Additionally, this variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). In summary, c.-160_-154dup meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): BA1, BP5.

Met criteria codes

• BA1: Minor allele frequency of 0.013 in gnomAD European Finnish population, 0.007 in European Non-Finnish, and 0.006 in Latinos
• BP5: Variant was found in a single family with a GCK variant. Cosegregation analysis and the phenotype of affected individuals showed the GCK variant to be the causative one.

Approved on: 2022-04-12

Published on: 2022-07-12