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.83C>T (p.Ala28Val)

CA9870161

994900 (ClinVar)

Gene: HNF4A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 5f405974-6734-4fb1-b726-0bb2f29895a5
Approved on: 2024-04-06
Published on: 2024-04-06

HGVS expressions

NM_175914.5:c.83C>T
NM_175914.5(HNF4A):c.83C>T (p.Ala28Val)
NC_000020.11:g.44406091C>T
CM000682.2:g.44406091C>T
NC_000020.10:g.43034731C>T
CM000682.1:g.43034731C>T
NC_000020.9:g.42468145C>T
NG_009818.1:g.55291C>T
ENST00000316673.9:c.83C>T
ENST00000316099.10:c.149C>T
ENST00000619550.5:c.123C>T
ENST00000681977.1:c.125C>T
ENST00000682169.1:c.102C>T
ENST00000683148.1:n.125C>T
ENST00000683657.1:n.125C>T
ENST00000684046.1:c.125C>T
ENST00000684136.1:c.125C>T
ENST00000684476.1:c.106C>T
ENST00000316099.9:c.149C>T
ENST00000316099.8:c.149C>T
ENST00000316673.8:c.83C>T
ENST00000372920.1:c.240C>T
ENST00000415691.2:c.149C>T
ENST00000443598.6:c.149C>T
ENST00000457232.5:c.83C>T
ENST00000609262.5:c.74C>T
ENST00000609795.5:c.83C>T
ENST00000619550.4:c.74C>T
NM_000457.4:c.149C>T
NM_001030003.2:c.83C>T
NM_001030004.2:c.83C>T
NM_001258355.1:c.128C>T
NM_001287182.1:c.74C>T
NM_001287183.1:c.74C>T
NM_001287184.1:c.74C>T
NM_175914.4:c.83C>T
NM_178849.2:c.149C>T
NM_178850.2:c.149C>T
NM_001030003.3:c.83C>T
NM_001030004.3:c.83C>T
NM_001258355.2:c.128C>T
NM_001287182.2:c.74C>T
NM_001287184.2:c.74C>T
NM_178849.3:c.149C>T
NM_178850.3:c.149C>T
NM_000457.5:c.149C>T
NM_000457.6:c.149C>T
NM_001287183.2:c.74C>T
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Uncertain Significance

Met criteria codes 1
BS2
Not Met criteria codes 3
PP4 PP3 PM2

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.83C>T variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, causes an amino acid change of alanine to valine at codon 28 (p.(Ala28Val)) of NM_175914.5. This variant was identified in a normoglycemic individual >70 years old, and the expected penetrance for HNF4A-MODY is 95% by age 70 (internal lab contributor) (BS2). The Grpmax filtering allele frequency of the c.83C>T variant in gnomAD v2.1.1 is 0.0007020%, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. This variant has a REVEL score of 0.186, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF4A function. This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (internal lab contributor). In summary, c.83C>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 8/11/2023): BS2.
Met criteria codes
BS2
This variant was identified in a normoglycemic individual >70 years old, and the expected penetrance for HNF4A-MODY is 95% by age 70 (internal lab contributor) (BS2).
Not Met criteria codes
PP4
This variant was identified in an individual with diabetes; however, the calculated MODY probability is <50% (internal lab contributor).
PP3
This variant has a REVEL score of 0.186, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF4A function.
PM2
The Popmax filtering allele frequency of the c.83C>T variant in gnomAD v2.1.1 is 0.0007020%, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
Curation History
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