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 computed assertion could be determined for this classification!

Variant: NM_175914.5(HNF4A):c.906C>T (p.Asn302=)

CA9870405

435435 (ClinVar)

Gene: HNF4A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 19af31eb-06cb-45d1-bd67-8d780a597cec
Approved on: 2024-12-02
Published on: 2024-12-02

HGVS expressions

NM_175914.5:c.906C>T
NM_175914.5(HNF4A):c.906C>T (p.Asn302=)
NC_000020.11:g.44424097C>T
CM000682.2:g.44424097C>T
NC_000020.10:g.43052737C>T
CM000682.1:g.43052737C>T
NC_000020.9:g.42486151C>T
NG_009818.1:g.73297C>T
ENST00000316673.9:c.906C>T
ENST00000316099.10:c.972C>T
ENST00000619550.5:c.946C>T
ENST00000316099.9:c.972C>T
ENST00000316099.8:c.972C>T
ENST00000316673.8:c.906C>T
ENST00000372920.1:c.*739C>T
ENST00000415691.2:c.972C>T
ENST00000443598.6:c.972C>T
ENST00000457232.5:c.906C>T
ENST00000609795.5:c.906C>T
ENST00000619550.4:c.897C>T
NM_000457.4:c.972C>T
NM_001030003.2:c.906C>T
NM_001030004.2:c.906C>T
NM_001258355.1:c.951C>T
NM_001287182.1:c.897C>T
NM_001287183.1:c.897C>T
NM_001287184.1:c.897C>T
NM_175914.4:c.906C>T
NM_178849.2:c.972C>T
NM_178850.2:c.972C>T
NM_001030003.3:c.906C>T
NM_001030004.3:c.906C>T
NM_001258355.2:c.951C>T
NM_001287182.2:c.897C>T
NM_001287184.2:c.897C>T
NM_178849.3:c.972C>T
NM_178850.3:c.972C>T
NM_000457.5:c.972C>T
NM_000457.6:c.972C>T
NM_001287183.2:c.897C>T
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 2
PM2 BS1

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.906C>T variant in the HNF4 homeobox A gene, HNF4A, is a synonymous variant at codon 302 (p.(Asn302=)) of NM_175914.5.This variant is not predicted by SpliceAI to impact splicing (SpliceAI score of 0.001 for donor loss, which is less than the MDEP cutoff of 0.2) and is not highly conserved (phyloP100way score of -2.537, which is below the MDEP cutoff of 2.0) (BP4, BP7). The Grpmax filtering allele frequency of the c.906C>T variant in gnomAD v2.1.1 is 0.000011, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. In summary, c.906C>T meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BP4, BP7.
Met criteria codes
BP4
The computational splicing predictor SpliceAI gives a score of 0.00 for donor loss, suggesting that the variant has no impact on splicing
BP7
This variant is not predicted by SpliceAI to impact splicing (SpliceAI score of 0.00 for donor loss, which is less than the MDEP cutoff of 0.2) and is not highly conserved (phyloP100way score of -2.537, which is below the MDEP cutoff of 2.0)/
Not Met criteria codes
PM2
The Grpmax filtering allele frequency of the c.906C>T variant in gnomAD v2.1.1 is 0.000011, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
BS1
The Grpmax filtering allele frequency of the c.906C>T variant in gnomAD v2.1.1 is 0.000011, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied.
Curation History
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