Variant: NM_175914.5(HNF4A):c.660_662delinsTCAA (p.Leu221fs)

CA213966

36356 (ClinVar)

Gene: HNF4A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

UUID: b0df1f17-5834-40c0-aa7b-36bdc16a1665

HGVS expressions

NM_175914.5:c.660_662delinsTCAA
NM_175914.5(HNF4A):c.660_662delinsTCAA (p.Leu221fs)
NC_000020.11:g.44418502_44418504delinsTCAA
CM000682.2:g.44418502_44418504delinsTCAA
NC_000020.10:g.43047142_43047144delinsTCAA
CM000682.1:g.43047142_43047144delinsTCAA
NC_000020.9:g.42480556_42480558delinsTCAA
NG_009818.1:g.67702_67704delinsTCAA
ENST00000316099.10:c.726_728delinsTCAA
ENST00000619550.5:n.700_702delinsTCAA
ENST00000683148.1:n.702_704delinsTCAA
ENST00000683657.1:n.1850_1852delinsTCAA
ENST00000316099.9:c.726_728delinsTCAA
ENST00000316099.8:c.726_728delinsTCAA
ENST00000316673.8:c.660_662delinsTCAA
ENST00000372920.1:c.*493_*495delinsTCAA
ENST00000415691.2:c.726_728delinsTCAA
ENST00000443598.6:c.726_728delinsTCAA
ENST00000457232.5:c.660_662delinsTCAA
ENST00000609795.5:c.660_662delinsTCAA
ENST00000619550.4:c.651_653delinsTCAA
NM_000457.4:c.726_728delinsTCAA
NM_001030003.2:c.660_662delinsTCAA
NM_001030004.2:c.660_662delinsTCAA
NM_001258355.1:c.705_707delinsTCAA
NM_001287182.1:c.651_653delinsTCAA
NM_001287183.1:c.651_653delinsTCAA
NM_001287184.1:c.651_653delinsTCAA
NM_175914.4:c.660_662delinsTCAA
NM_178849.2:c.726_728delinsTCAA
NM_178850.2:c.726_728delinsTCAA
NM_001030003.3:c.660_662delinsTCAA
NM_001030004.3:c.660_662delinsTCAA
NM_001258355.2:c.705_707delinsTCAA
NM_001287182.2:c.651_653delinsTCAA
NM_001287184.2:c.651_653delinsTCAA
NM_178849.3:c.726_728delinsTCAA
NM_178850.3:c.726_728delinsTCAA
NM_000457.5:c.726_728delinsTCAA
NM_000457.6:c.726_728delinsTCAA
NM_001287183.2:c.651_653delinsTCAA

Likely Pathogenic

• Met criteria codes: 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 for HNF4A Version 1.0.0

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.660_662delGCTinsTCAA (p.(Leu221GInfsTer6)) variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, 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). In summary, c.660_662delGCTinsTCAA (p.(Leu221GInfsTer6)) meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.0.0, approved 11/16/2022): PVS1, PM2_Supporting.

Met criteria codes

• PVS1: Predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1, PMID: 23348805).
• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

Approved on: 2023-05-27

Published on: 2023-05-27