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

CA1703634895

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: acd20f90-3ec6-4278-bcc7-75baa9f11c96

HGVS expressions

NM_033508.3:c.808_810del

NC_000007.14:g.44147703_44147705del

CM000669.2:g.44147703_44147705del

NC_000007.13:g.44187302_44187304del

CM000669.1:g.44187302_44187304del

NC_000007.12:g.44153827_44153829del

NG_008847.1:g.46722_46724del

NG_008847.2:g.55469_55471del

ENST00000395796.8:c.*809_*811del

ENST00000616242.5:c.811_813del

ENST00000345378.7:c.814_816del

ENST00000403799.8:c.811_813del

ENST00000671824.1:c.811_813del

ENST00000673284.1:c.811_813del

ENST00000345378.6:c.814_816del

ENST00000395796.7:c.808_810del

ENST00000403799.7:c.811_813del

ENST00000437084.1:c.760_762del

ENST00000616242.4:c.808_810del

NM_000162.3:c.811_813del

NM_033507.1:c.814_816del

NM_033508.1:c.808_810del

NM_000162.4:c.811_813del

NM_001354800.1:c.811_813del

NM_033507.2:c.814_816del

NM_033508.2:c.808_810del

NM_000162.5:c.811_813del

NM_033507.3:c.814_816del

Uncertain Significance

PM2_Supporting PP4 PM4_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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.811_813del variant in the glucokinase gene, GCK, is a 3 base pair deletion resulting in the in-frame deletion of 1 amino acid at codon 271 (p.(Leu271del)) within exon 7 of NM_000162.5. This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (HbA1c between 5.6-7.6% and fasting glucose between 5.5-8mmol/L) (PP4; internal lab contributor). This variant is absent in gnomAD v2.1.1 (PM2_Supporting).The c.811_813del variant is predicted to change the length of the protein due to an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting). In summary, c.811_813del meets the criteria to be classified as a variant of uncertain signficance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PP4, PM2_Supporting, PM4_Supporting.

PM2_Supporting

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

PP4

This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (HbA1c between 5.6-7.6% and fasting glucose between 5.5-8mmol/L) (PP4; internal lab contributor).

PM4_Supporting

The c.811_813del variant is predicted to change the length of the protein due to an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting).

Approved on: 2023-12-15

Published on: 2023-12-15

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.