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]

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Variant: NM_000162.5(GCK):c.427_428delinsCT (p.Lys143Leu)

CA658655971

451690 (ClinVar)

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: f13fd1c2-ec28-46b0-9742-4d0ce87c44d4

Approved on: 2024-03-22

Published on: 2024-03-22

HGVS expressions

NM_000162.5:c.427_428delinsCT

NM_000162.5(GCK):c.427_428delinsCT (p.Lys143Leu)

NC_000007.14:g.44151011_44151012delinsAG

CM000669.2:g.44151011_44151012delinsAG

NC_000007.13:g.44190610_44190611delinsAG

CM000669.1:g.44190610_44190611delinsAG

NC_000007.12:g.44157135_44157136delinsAG

NG_008847.1:g.43412_43413delinsCT

NG_008847.2:g.52159_52160delinsCT

ENST00000395796.8:c.*425_*426delinsCT

ENST00000616242.5:c.427_428delinsCT

ENST00000682635.1:n.913_914delinsCT

ENST00000345378.7:c.430_431delinsCT

ENST00000403799.8:c.427_428delinsCT

ENST00000671824.1:c.427_428delinsCT

ENST00000673284.1:c.427_428delinsCT

ENST00000345378.6:c.430_431delinsCT

ENST00000395796.7:c.424_425delinsCT

ENST00000403799.7:c.427_428delinsCT

ENST00000437084.1:c.376_377delinsCT

ENST00000616242.4:c.424_425delinsCT

NM_000162.3:c.427_428delinsCT

NM_033507.1:c.430_431delinsCT

NM_033508.1:c.424_425delinsCT

NM_000162.4:c.427_428delinsCT

NM_001354800.1:c.427_428delinsCT

NM_033507.2:c.430_431delinsCT

NM_033508.2:c.424_425delinsCT

NM_033507.3:c.430_431delinsCT

NM_033508.3:c.424_425delinsCT

Uncertain Significance

PM2_Supporting PP3 PP2

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.427_428delinsCT variant in the glucokinase gene, GCK, causes an amino acid change of lysine to leucine at codon 143 (p.(Lys143Leu)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a Polyphen result of deleterious and Grantham distance of 107 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.427_428delinsCT meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0 approved 8/11/2023): PM2_Supporting, PP2, PP3.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Absent from gnomAD v4.0.0

PP3

This variant is predicted to be deleterious by computational evidence, with a Polyphen result of deleterious and Grantham distance of 107 (PP3).

PP2

GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2).

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