Variant: NM_175914.5(HNF4A):c.826+30dup

Version: 1.0
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CA213988

36361 (ClinVar)

Gene: HNF4A (HGNC:3172)

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: b608dd9d-67f7-4b31-92c8-3fbbcea20586

Approved on: 2024-12-02

Published on: 2024-12-02

HGVS expressions

NM_175914.5:c.826+30dup
NM_175914.5(HNF4A):c.826+30dup
NC_000020.11:g.44419906dup
CM000682.2:g.44419906dup
NC_000020.10:g.43048546dup
CM000682.1:g.43048546dup
NC_000020.9:g.42481960dup
NG_009818.1:g.69106dup
ENST00000316673.9:c.826+30dup
ENST00000316099.10:c.892+30dup
ENST00000619550.5:c.866+30dup
ENST00000683148.1:n.868+30dup
ENST00000683657.1:n.2046dup
ENST00000316099.9:c.892+30dup
ENST00000316099.8:c.892+30dup
ENST00000316673.8:c.826+30dup
ENST00000372920.1:c.*659+30dup
ENST00000415691.2:c.892+30dup
ENST00000443598.6:c.892+30dup
ENST00000457232.5:c.826+30dup
ENST00000609795.5:c.826+30dup
ENST00000619550.4:c.817+30dup
NM_000457.4:c.892+30dup
NM_001030003.2:c.826+30dup
NM_001030004.2:c.826+30dup
NM_001258355.1:c.871+30dup
NM_001287182.1:c.817+30dup
NM_001287183.1:c.817+30dup
NM_001287184.1:c.817+30dup
NM_175914.4:c.826+30dup
NM_178849.2:c.892+30dup
NM_178850.2:c.892+30dup
NM_001030003.3:c.826+30dup
NM_001030004.3:c.826+30dup
NM_001258355.2:c.871+30dup
NM_001287182.2:c.817+30dup
NM_001287184.2:c.817+30dup
NM_178849.3:c.892+30dup
NM_178850.3:c.892+30dup
NM_000457.5:c.892+30dup
NM_000457.6:c.892+30dup
NM_001287183.2:c.817+30dup

Benign

• Met criteria codes: BA1 PP4

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF4A Version 2.0.0

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.826+30dup variant in the HNF4 homeobox A gene, HNF4A, is a single nucleotide insertion within intron 7 of NM_175914.5. This variant was identified in an individual with a clinical history suggestive of HNF4A-MODY (neonatal hypoglycemia that is responsive to diazoxide and negative genetic testing for ABCC8, KCNJ11, HNF1A, GLUD1, and HADH) (PP4; internal lab contributors). However, this variant has a Grpmax Filtering allele frequency in gnomAD 2.1.1 of 0.0005686, which is greater than the MDEP threshold for BA1 (0.0001) (BA1). In summary, c.826+30dup meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BA1, PP4.

Met criteria codes

• BA1: This variant has a Grpmax Filtering allele frequency in gnomAD v2.1.1 of 0.0005686, which is greater than the MDEP threshold for BA1 (0.0001) (BA1).
• PP4: This variant was identified in an individual with a clinical history suggestive of HNF4A-MODY (neonatal hypoglycemia that is responsive to diazoxide and negative genetic testing for ABCC8, KCNJ11, HNF1A, GLUD1, and HADH) (PP4; internal lab contributors).