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.178del

CA2580612100

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 5af5457e-1ea5-4c61-b739-672736fbcc47

HGVS expressions

NM_001354803.2:c.178del

NC_000007.14:g.44145606del

CM000669.2:g.44145606del

NC_000007.13:g.44185205del

CM000669.1:g.44185205del

NC_000007.12:g.44151730del

NG_008847.1:g.48818del

NG_008847.2:g.57565del

ENST00000395796.8:c.*1142del

ENST00000616242.5:c.*264del

ENST00000683378.1:n.370del

ENST00000336642.9:c.178del

ENST00000345378.7:c.1147del

ENST00000403799.8:c.1144del

ENST00000671824.1:c.1207del

ENST00000672743.1:n.156del

ENST00000673284.1:c.1144del

ENST00000336642.8:c.196del

ENST00000345378.6:c.1147del

ENST00000395796.7:c.1141del

ENST00000403799.7:c.1144del

ENST00000437084.1:c.1093del

ENST00000459642.1:n.524del

ENST00000616242.4:c.1141del

NM_000162.3:c.1144del

NM_033507.1:c.1147del

NM_033508.1:c.1141del

NM_000162.4:c.1144del

NM_001354800.1:c.1144del

NM_001354801.1:c.133del

NM_001354802.1:c.4del

NM_001354803.1:c.178del

NM_033507.2:c.1147del

NM_033508.2:c.1141del

NM_000162.5:c.1144del

NM_033507.3:c.1147del

NM_033508.3:c.1141del

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.1144del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 382 in NM_000162.4), adding 20 novel amino acids before encountering a stop codon (p.(Cys382Alafs*20)). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). While this variant, located in exon 10 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where loss-of-function is an established disease mechanism (PVS1; PMID: 19790256). In summary, c.1144del 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

While this variant, located in exon 10 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where 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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