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.1163dup (p.Val389fs)

CA10603030

280892 (ClinVar)

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 7adefff0-520c-4370-b35b-177b1d27873f

HGVS expressions

NM_000162.5:c.1163dup

NM_000162.5(GCK):c.1163dup (p.Val389fs)

NC_000007.14:g.44145589dup

CM000669.2:g.44145589dup

NC_000007.13:g.44185188dup

CM000669.1:g.44185188dup

NC_000007.12:g.44151713dup

NG_008847.1:g.48837dup

NG_008847.2:g.57584dup

ENST00000395796.8:c.*1161dup

ENST00000616242.5:c.*283dup

ENST00000683378.1:n.389dup

ENST00000336642.9:c.197dup

ENST00000345378.7:c.1166dup

ENST00000403799.8:c.1163dup

ENST00000671824.1:c.1226dup

ENST00000672743.1:n.175dup

ENST00000673284.1:c.1163dup

ENST00000336642.8:c.215dup

ENST00000345378.6:c.1166dup

ENST00000395796.7:c.1160dup

ENST00000403799.7:c.1163dup

ENST00000437084.1:c.1112dup

ENST00000459642.1:n.543dup

ENST00000616242.4:c.1160dup

NM_000162.3:c.1163dup

NM_033507.1:c.1166dup

NM_033508.1:c.1160dup

NM_000162.4:c.1163dup

NM_001354800.1:c.1163dup

NM_001354801.1:c.152dup

NM_001354802.1:c.23dup

NM_001354803.1:c.197dup

NM_033507.2:c.1166dup

NM_033508.2:c.1160dup

NM_033507.3:c.1166dup

NM_033508.3:c.1160dup

NM_001354803.2:c.197dup

Likely Pathogenic

PM2_Supporting PVS1

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.1163dup variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 389 in NM_000162.5, adding 70 novel amino acids before encountering a stop codon (p.(Val389ArgfsTer70)). 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). In summary, c.1163dup 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).

Approved on: 2024-04-28

Published on: 2024-04-28

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