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.1133_1149del (p.Ala378fs)

CA658655962

447381 (ClinVar)

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 7bc5303a-12cb-452b-bf1d-39f3bc4b2c4f

HGVS expressions

NM_000162.5:c.1133_1149del

NM_000162.5(GCK):c.1133_1149del (p.Ala378fs)

NC_000007.14:g.44145603_44145619del

CM000669.2:g.44145603_44145619del

NC_000007.13:g.44185202_44185218del

CM000669.1:g.44185202_44185218del

NC_000007.12:g.44151727_44151743del

NG_008847.1:g.48807_48823del

NG_008847.2:g.57554_57570del

ENST00000395796.8:c.*1131_*1147del

ENST00000616242.5:c.*253_*269del

ENST00000683378.1:n.359_375del

ENST00000336642.9:c.167_183del

ENST00000345378.7:c.1136_1152del

ENST00000403799.8:c.1133_1149del

ENST00000671824.1:c.1196_1212del

ENST00000672743.1:n.145_161del

ENST00000673284.1:c.1133_1149del

ENST00000336642.8:c.185_201del

ENST00000345378.6:c.1136_1152del

ENST00000395796.7:c.1130_1146del

ENST00000403799.7:c.1133_1149del

ENST00000437084.1:c.1082_1098del

ENST00000459642.1:n.513_529del

ENST00000616242.4:c.1130_1146del

NM_000162.3:c.1133_1149del

NM_033507.1:c.1136_1152del

NM_033508.1:c.1130_1146del

NM_000162.4:c.1133_1149del

NM_001354800.1:c.1133_1149del

NM_001354801.1:c.122_138del

NM_001354802.1:c.-8_9del

NM_001354803.1:c.167_183del

NM_033507.2:c.1136_1152del

NM_033508.2:c.1130_1146del

NM_033507.3:c.1136_1152del

NM_033508.3:c.1130_1146del

NM_001354803.2:c.167_183del

Likely Pathogenic

PVS1 PM2_Supporting

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.1133_1149del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 378 (NM_000162.5), adding 75 novel amino acids before encountering a stop codon (p.(Ala378GlyfsTer75)). 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). In summary, c.1133_1149del 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.

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).

PM2_Supporting

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

Approved on: 2024-01-22

Published on: 2024-01-22

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