The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: GCK vs undefined
  • No ClinVar Id was directly found from the curated document
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_033508.3:c.861-7T>G

CA2850445536

Gene: GCK
Condition: monogenic diabetes
Inheritance Mode: Semidominant inheritance
UUID: 3166029d-0b6c-479b-97fb-b9b9d3711fe4
Approved on: 2025-06-02
Published on: 2025-06-02

HGVS expressions

NM_033508.3:c.861-7T>G
NC_000007.14:g.44146625A>C
CM000669.2:g.44146625A>C
NC_000007.13:g.44186224A>C
CM000669.1:g.44186224A>C
NC_000007.12:g.44152749A>C
NG_008847.1:g.47799T>G
NG_008847.2:g.56546T>G
ENST00000395796.8:c.*862-7T>G
ENST00000616242.5:c.854-7T>G
ENST00000683378.1:n.83T>G
ENST00000345378.7:c.867-7T>G
ENST00000403799.8:c.864-7T>G
ENST00000671824.1:c.927-7T>G
ENST00000673284.1:c.864-7T>G
ENST00000345378.6:c.867-7T>G
ENST00000395796.7:c.861-7T>G
ENST00000403799.7:c.864-7T>G
ENST00000437084.1:c.813-7T>G
ENST00000473353.1:n.162-7T>G
ENST00000616242.4:c.861-7T>G
NM_000162.3:c.864-7T>G
NM_033507.1:c.867-7T>G
NM_033508.1:c.861-7T>G
NM_000162.4:c.864-7T>G
NM_001354800.1:c.864-7T>G
NM_001354801.1:c.2T>G
NM_033507.2:c.867-7T>G
NM_033508.2:c.861-7T>G
NM_000162.5:c.864-7T>G
NM_033507.3:c.867-7T>G
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Uncertain Significance

Met criteria codes 2
PP3 PM2_Supporting
Not Met criteria codes 2
PS1 PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.864-7T>G variant in the glucokinase gene, GCK, is a single nucleotide variant within intron 7 of NM_000162.5. This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.98 for acceptor gain, predicting that the variant disrupts the acceptor site of intron 7 of GCK (PP3). PS1_Supporting cannot be applied, as the nucleotide change c.864-7T>A, which is predicted to disrupt the intron 7 splice acceptor site to a lesser extent than c.864-7T>G, has not met the criteria to be classified as pathogenic for monogenic diabetes by the ClinGen MDEP. While this variant was identified in an individual with a phenotype suggestive of GCK-hyperglycemia, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributors). In summary, c.864-7T>G meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 2/17/2025): PM2_Supporting, PP3.
Met criteria codes
PP3
The computational splicing predictor SpliceAI gives a score of 0.98 for acceptor gain, predicting that the variant disrupts the acceptor site of intron 7 of GCK (PP3).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting).
Not Met criteria codes
PS1
PS1_Supporting cannot be applied, as the nucleotide change c.864-7T>A, which is predicted to disrupt the intron 7 splice acceptor site to a similar extent as c.864-7T>G, has not met the criteria to be classified as pathogenic for monogenic diabetes by the ClinGen MDEP.
PP4
While this variant was identified in individuals with a phenotype suggestive of GCK-hyperglycemia, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributor).
Curation History
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