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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001354803.2:c.203del

CA2580610955

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 92e277c9-2bed-4781-8f1e-be52b90829bd

HGVS expressions

NM_001354803.2:c.203del

NC_000007.14:g.44145581del

CM000669.2:g.44145581del

NC_000007.13:g.44185180del

CM000669.1:g.44185180del

NC_000007.12:g.44151705del

NG_008847.1:g.48843del

NG_008847.2:g.57590del

ENST00000395796.8:c.*1167del

ENST00000616242.5:c.*289del

ENST00000683378.1:n.395del

ENST00000336642.9:c.203del

ENST00000345378.7:c.1172del

ENST00000403799.8:c.1169del

ENST00000671824.1:c.1232del

ENST00000672743.1:n.181del

ENST00000673284.1:c.1169del

ENST00000336642.8:c.221del

ENST00000345378.6:c.1172del

ENST00000395796.7:c.1166del

ENST00000403799.7:c.1169del

ENST00000437084.1:c.1118del

ENST00000459642.1:n.549del

ENST00000616242.4:c.1166del

NM_000162.3:c.1169del

NM_033507.1:c.1172del

NM_033508.1:c.1166del

NM_000162.4:c.1169del

NM_001354800.1:c.1169del

NM_001354801.1:c.158del

NM_001354802.1:c.29del

NM_001354803.1:c.203del

NM_033507.2:c.1172del

NM_033508.2:c.1166del

NM_000162.5:c.1169del

NM_033507.3:c.1172del

NM_033508.3:c.1166del

Likely Pathogenic

PM2_Supporting PVS1

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 GCK Version 1.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1169del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 290 in NM_000162.5, adding 12 novel amino acids before encountering a stop codon (p.(Ile390ThrfsTer12)). This variant, located in biologically relevant exon 9 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: 19790256). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a phenotype suggestive of GCK-hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributors). In summary, c.1169del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PVS1, PM2_supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting). gnomAD v4.0.0: absent

PVS1

This variant, located in biologically-relevant exon 9 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: 19790256).

PP4

This variant was identified in an individual with a phenotype suggestive of GCK-hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributors).

Approved on: 2024-04-28

Published on: 2024-04-28

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