Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_175914.5(HNF4A):c.50-4791_50-4788del

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10643872

338422 (ClinVar)

Gene: HNF4A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c86bf0a1-a577-41ec-afe4-5bc4c23fb23e

Approved on: 2025-01-29

Published on: 2025-01-29

HGVS expressions

NM_175914.5:c.50-4791_50-4788del

NM_175914.5(HNF4A):c.50-4791_50-4788del

NC_000020.11:g.44401267_44401270del

CM000682.2:g.44401267_44401270del

NC_000020.10:g.43029907_43029910del

CM000682.1:g.43029907_43029910del

NC_000020.9:g.42463321_42463324del

NG_009818.1:g.50467_50470del

ENST00000316673.9:c.50-4791_50-4788del

ENST00000316099.10:c.-106_-103del

ENST00000316099.9:c.-106_-103del

ENST00000316673.8:c.50-4791_50-4788del

ENST00000457232.5:c.50-4791_50-4788del

ENST00000609262.5:c.41-4791_41-4788del

ENST00000609795.5:c.50-4791_50-4788del

ENST00000619550.4:c.41-4791_41-4788del

NM_000457.4:c.-106_-103del

NM_001030003.2:c.50-4791_50-4788del

NM_001030004.2:c.50-4791_50-4788del

NM_001258355.1:c.-218_-215del

NM_001287182.1:c.41-4791_41-4788del

NM_001287183.1:c.41-4791_41-4788del

NM_001287184.1:c.41-4791_41-4788del

NM_175914.4:c.50-4791_50-4788del

NM_178849.2:c.-106_-103del

NM_178850.2:c.-106_-103del

NM_001030003.3:c.50-4791_50-4788del

NM_001030004.3:c.50-4791_50-4788del

NM_001258355.2:c.-218_-215del

NM_001287182.2:c.41-4791_41-4788del

NM_001287184.2:c.41-4791_41-4788del

NM_178849.3:c.-106_-103del

NM_178850.3:c.-106_-103del

NM_000457.5:c.-106_-103del

NM_000457.6:c.-106_-103del

NM_001287183.2:c.41-4791_41-4788del

Uncertain Significance

PM2_Supporting BP4

PP3

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.50-4791_50-4788del variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, is a 4-nucleotide-deletion within intron 1 of NM_175914.5. The computational splicing predictor SpliceAI gives a score of 0.00 for donor and acceptor loss, suggesting that the variant has no impact on splicing (BP4). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.50-4791_50-4788del meets the criteria to be classified as VUS for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BP4, PM2_Supporting.

PM2_Supporting

Absent in gnomAD

BP4

The computational splicing predictor SpliceAI gives a score of 0.00 for donor and acceptor loss, suggesting that the variant has no impact on splicing (BP4).

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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