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_000162.5(GCK):c.1054del (p.Ile351_Leu352insTer)

CA891843077

585907 (ClinVar)

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 2e22ba56-4fc2-4df8-bc5c-d2d20c564281

HGVS expressions

NM_000162.5:c.1054del

NM_000162.5(GCK):c.1054del (p.Ile351_Leu352insTer)

NC_000007.14:g.44145697del

CM000669.2:g.44145697del

NC_000007.13:g.44185296del

CM000669.1:g.44185296del

NC_000007.12:g.44151821del

NG_008847.1:g.48728del

NG_008847.2:g.57475del

ENST00000395796.8:c.*1052del

ENST00000616242.5:c.*174del

ENST00000683378.1:n.280del

ENST00000336642.9:c.88del

ENST00000345378.7:c.1057del

ENST00000403799.8:c.1054del

ENST00000671824.1:c.1117del

ENST00000672743.1:n.66del

ENST00000673284.1:c.1054del

ENST00000336642.8:c.106del

ENST00000345378.6:c.1057del

ENST00000395796.7:c.1051del

ENST00000403799.7:c.1054del

ENST00000437084.1:c.1003del

ENST00000459642.1:n.434del

ENST00000473353.1:n.352del

ENST00000616242.4:c.1051del

NM_000162.3:c.1054del

NM_033507.1:c.1057del

NM_033508.1:c.1051del

NM_000162.4:c.1054del

NM_001354800.1:c.1054del

NM_001354801.1:c.43del

NM_001354802.1:c.-87del

NM_001354803.1:c.88del

NM_033507.2:c.1057del

NM_033508.2:c.1051del

NM_033507.3:c.1057del

NM_033508.3:c.1051del

NM_001354803.2:c.88del

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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1054del variant in the glucokinase gene, GCK, results in a premature termination at codon 352 (p.Leu352Ter) of NM_000162.5. 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 in 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.1054del 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).

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: 2024-03-31

Published on: 2024-03-31

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