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.346_348del

CA2017997767

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 84ab9cd7-26af-44a1-bcdd-7c9e2a313f34

HGVS expressions

NM_001354803.2:c.346_348del

NC_000007.14:g.44145221_44145223del

CM000669.2:g.44145221_44145223del

NC_000007.13:g.44184820_44184822del

CM000669.1:g.44184820_44184822del

NC_000007.12:g.44151345_44151347del

NG_008847.1:g.49202_49204del

NG_008847.2:g.57949_57951del

ENST00000395796.8:c.*1310_*1312del

ENST00000616242.5:c.*432_*434del

ENST00000683378.1:n.538_540del

ENST00000336642.9:c.346_348del

ENST00000345378.7:c.1315_1317del

ENST00000403799.8:c.1312_1314del

ENST00000671824.1:c.1375_1377del

ENST00000672743.1:n.324_326del

ENST00000673284.1:c.1312_1314del

ENST00000336642.8:n.364_366del

ENST00000345378.6:c.1315_1317del

ENST00000395796.7:c.1309_1311del

ENST00000403799.7:c.1312_1314del

ENST00000437084.1:c.1261_1263del

ENST00000459642.1:n.692_694del

ENST00000616242.4:n.1309_1311del

NM_000162.3:c.1312_1314del

NM_033507.1:c.1315_1317del

NM_033508.1:c.1309_1311del

NM_000162.4:c.1312_1314del

NM_001354800.1:c.1312_1314del

NM_001354801.1:c.301_303del

NM_001354802.1:c.172_174del

NM_001354803.1:c.346_348del

NM_033507.2:c.1315_1317del

NM_033508.2:c.1309_1311del

NM_000162.5:c.1312_1314del

NM_033507.3:c.1315_1317del

NM_033508.3:c.1309_1311del

Uncertain Significance

PM4_Supporting 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.1312_1314del variant in the glucokinase gene, GCK, is a three base pair deletion resulting in the in-frame deletion of one amino acid codon 438 (p.(Phe438del)) within exon 10 of NM_000162.5. The c.1312_1314del variant is predicted to change the length of the protein due an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting), and was identified in an individual with a clinical history suggestive of GCK-MODY; however, PP4 could not be evaluated due to insufficient clinical information (internal lab contributor). In summary, the c.1312_1314del variant 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 1.2.0, approved 6/7/2023): PM2_Supporting, PM4_Supporting.

PM4_Supporting

The c.1312_1314del variant is predicted to change the length of the protein due an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting).

PM2_Supporting

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

PS4

This variant was identified in an individual with a clinical picture consistent with monogenic diabetes, however PS4_Moderate cannot be applied because this number is below the MDEP threshold (internal lab contributor)

PP4

This variant was identified in an individual with a clinical history suggestive of GCK-MODY; however, PP4 could not be evaluated due to insufficient clinical information.

Approved on: 2023-06-20

Published on: 2023-06-20

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