Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_175914.5(HNF4A):c.932G>T (p.Arg311Leu)

CA409108272

2018786 (ClinVar)

Gene: HNF4A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ea865f61-383f-47e1-8efe-a7acf40ecad6
Approved on: 2024-07-31
Published on: 2024-07-31

HGVS expressions

NM_175914.5:c.932G>T
NM_175914.5(HNF4A):c.932G>T (p.Arg311Leu)
NC_000020.11:g.44424123G>T
CM000682.2:g.44424123G>T
NC_000020.10:g.43052763G>T
CM000682.1:g.43052763G>T
NC_000020.9:g.42486177G>T
NG_009818.1:g.73323G>T
ENST00000316673.9:c.932G>T
ENST00000316099.10:c.998G>T
ENST00000619550.5:c.972G>T
ENST00000316099.9:c.998G>T
ENST00000316099.8:c.998G>T
ENST00000316673.8:c.932G>T
ENST00000372920.1:c.*765G>T
ENST00000415691.2:c.998G>T
ENST00000443598.6:c.998G>T
ENST00000457232.5:c.932G>T
ENST00000609795.5:c.932G>T
ENST00000619550.4:c.923G>T
NM_000457.4:c.998G>T
NM_001030003.2:c.932G>T
NM_001030004.2:c.932G>T
NM_001258355.1:c.977G>T
NM_001287182.1:c.923G>T
NM_001287183.1:c.923G>T
NM_001287184.1:c.923G>T
NM_175914.4:c.932G>T
NM_178849.2:c.998G>T
NM_178850.2:c.998G>T
NM_001030003.3:c.932G>T
NM_001030004.3:c.932G>T
NM_001258355.2:c.977G>T
NM_001287182.2:c.923G>T
NM_001287184.2:c.923G>T
NM_178849.3:c.998G>T
NM_178850.3:c.998G>T
NM_000457.5:c.998G>T
NM_000457.6:c.998G>T
NM_001287183.2:c.923G>T
More

Likely Pathogenic

Met criteria codes 5
PM5_Strong PM2_Supporting PP4 PP3 PM1_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.932G>T variant in the HNF4 homeobox A gene, HNF4A, causes an amino acid change of arginine to leucine at codon 311 (p.(Arg311Leu)) of NM_175914.4. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.986, which is greater than the MDEP threshold of 0.70 (PP3). Two other missense variants, c.932G>A p.Arg311His and c.931C>T p.Arg311Cys, have been interpreted as pathogenic by the ClinGen MDEP and p.Arg311Leu has a greater Grantham distance than p.Arg311His (PM5_Strong). This variant was identified in an individual with a clinical history highly specific for HNF4A-MODY (MODY probability calculator result >50% and negative genetic testing for HNF1A) (PP4; internal lab contributors). In summary, c.932G>T 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 2.0.0, approved 10/11/2023): PM5_Strong, PP3, PP4, PM1_Supporting, PM2_Supporting.
Met criteria codes
PM5_Strong
Two other missense variants, c.932G>A p.Arg311His and c.931C>T p.Arg311Cys, have been interpreted as pathogenic by the ClinGen MDEP and p.Arg311Leu has a greater Grantham distance than p.Arg311His.
PM2_Supporting
Absent from gnomAD
PP4
This variant was identified in an individual with a clinical history highly specific for HNF4A-MODY (MODY probability calculator result >50% and negative genetic testing for HNF1A) (PP4; internal lab contributors).
PP3
REVEL 0.986
PM1_Supporting
This variant is located within the ligand-binding domain (codons 180-220 and 300-350) of HNF4A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.