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.331_334dup

CA1139771343

Gene: GCK

Condition: maturity-onset diabetes of the young type 2

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 37498f6f-0d5d-45e2-a398-d895c579b695

HGVS expressions

NM_001354803.2:c.331_334dup

NC_000007.14:g.44145234_44145237dup

CM000669.2:g.44145234_44145237dup

NC_000007.13:g.44184833_44184836dup

CM000669.1:g.44184833_44184836dup

NC_000007.12:g.44151358_44151361dup

NG_008847.1:g.49187_49190dup

NG_008847.2:g.57934_57937dup

ENST00000395796.8:c.*1295_*1298dup

ENST00000616242.5:c.*417_*420dup

ENST00000683378.1:n.523_526dup

ENST00000336642.9:c.331_334dup

ENST00000345378.7:c.1300_1303dup

ENST00000403799.8:c.1297_1300dup

ENST00000671824.1:c.1360_1363dup

ENST00000672743.1:n.309_312dup

ENST00000673284.1:c.1297_1300dup

ENST00000336642.8:c.349_352dup

ENST00000345378.6:c.1300_1303dup

ENST00000395796.7:c.1294_1297dup

ENST00000403799.7:c.1297_1300dup

ENST00000437084.1:c.1246_1249dup

ENST00000459642.1:n.677_680dup

ENST00000616242.4:c.1294_1297dup

NM_000162.3:c.1297_1300dup

NM_033507.1:c.1300_1303dup

NM_033508.1:c.1294_1297dup

NM_000162.4:c.1297_1300dup

NM_001354800.1:c.1297_1300dup

NM_001354801.1:c.286_289dup

NM_001354802.1:c.157_160dup

NM_001354803.1:c.331_334dup

NM_033507.2:c.1300_1303dup

NM_033508.2:c.1294_1297dup

NM_000162.5:c.1297_1300dup

NM_033507.3:c.1300_1303dup

NM_033508.3:c.1294_1297dup

Likely Pathogenic

PVS1 PM2_Supporting

PS4 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.1297_1300dup variant in the glucokinase gene, GCK, results in a premature termination at codon 434 (p.(Cys434Ter)) of NM_000162.5. 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). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributors). In summary, c.1297_1300dup 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)

PM2_Supporting

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

PS4

One case in Paris database (PS4_Moderate met at 4 cases)

PP4

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

Approved on: 2023-11-03

Published on: 2023-11-03

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