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.100del (p.Val34fs)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA658799362

524154 (ClinVar)

Gene: HNF4A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 14de735c-e1e7-4836-a9a3-4a9f83329388

Approved on: 2024-04-06

Published on: 2024-04-06

HGVS expressions

NM_175914.5:c.100del

NM_175914.5(HNF4A):c.100del (p.Val34fs)

NC_000020.11:g.44406108del

CM000682.2:g.44406108del

NC_000020.10:g.43034748del

CM000682.1:g.43034748del

NC_000020.9:g.42468162del

NG_009818.1:g.55308del

ENST00000316673.9:c.100del

ENST00000316099.10:c.166del

ENST00000619550.5:c.140del

ENST00000681977.1:c.142del

ENST00000682169.1:c.119del

ENST00000683148.1:n.142del

ENST00000683657.1:n.142del

ENST00000684046.1:c.142del

ENST00000684136.1:c.142del

ENST00000684476.1:c.123del

ENST00000316099.9:c.166del

ENST00000316099.8:c.166del

ENST00000316673.8:c.100del

ENST00000372920.1:c.257del

ENST00000415691.2:c.166del

ENST00000443598.6:c.166del

ENST00000457232.5:c.100del

ENST00000609262.5:c.91del

ENST00000609795.5:c.100del

ENST00000619550.4:c.91del

NM_000457.4:c.166del

NM_001030003.2:c.100del

NM_001030004.2:c.100del

NM_001258355.1:c.145del

NM_001287182.1:c.91del

NM_001287183.1:c.91del

NM_001287184.1:c.91del

NM_175914.4:c.100del

NM_178849.2:c.166del

NM_178850.2:c.166del

NM_001030003.3:c.100del

NM_001030004.3:c.100del

NM_001258355.2:c.145del

NM_001287182.2:c.91del

NM_001287184.2:c.91del

NM_178849.3:c.166del

NM_178850.3:c.166del

NM_000457.5:c.166del

NM_000457.6:c.166del

NM_001287183.2:c.91del

Likely Pathogenic

PM2_Supporting PVS1

PS4 PP4

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.100delG variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, causes a frameshift in the protein at codon 34 of NM_175914.5, adding 70 novel amino acids before encountering a stop codon (p.(Val34SerfsTer70)). This variant, located in biologically-relevant exon 2 of 10, 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 in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information and PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributor; ClinVar ID: 524154). In summary, c.100delG meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): PVS1, PM2_Supporting.

PM2_Supporting

This variant is absent in gnomAD v2.1.1 (PM2_Supporting).

PVS1

This variant, located in biologically-relevant exon 2 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805).

PS4

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

PP4

This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information (internal lab contributor; ClinVar ID: 524154).

Curation History

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