Evidence Repository
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 obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000162.5(GCK):c.1155dup (p.Leu386fs)

CA658655961

447385 (ClinVar)

Gene: GCK
Condition: monogenic diabetes
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: e5905d88-3825-47b8-8797-a858f985dd8a
Approved on: 2024-12-02
Published on: 2024-12-02

HGVS expressions

NM_000162.5:c.1155dup
NM_000162.5(GCK):c.1155dup (p.Leu386fs)
NC_000007.14:g.44145598dup
CM000669.2:g.44145598dup
NC_000007.13:g.44185197dup
CM000669.1:g.44185197dup
NC_000007.12:g.44151722dup
NG_008847.1:g.48829dup
NG_008847.2:g.57576dup
ENST00000395796.8:c.*1153dup
ENST00000616242.5:c.*275dup
ENST00000683378.1:n.381dup
ENST00000336642.9:c.189dup
ENST00000345378.7:c.1158dup
ENST00000403799.8:c.1155dup
ENST00000671824.1:c.1218dup
ENST00000672743.1:n.167dup
ENST00000673284.1:c.1155dup
ENST00000336642.8:c.207dup
ENST00000345378.6:c.1158dup
ENST00000395796.7:c.1152dup
ENST00000403799.7:c.1155dup
ENST00000437084.1:c.1104dup
ENST00000459642.1:n.535dup
ENST00000616242.4:c.1152dup
NM_000162.3:c.1155dup
NM_033507.1:c.1158dup
NM_033508.1:c.1152dup
NM_000162.4:c.1155dup
NM_001354800.1:c.1155dup
NM_001354801.1:c.144dup
NM_001354802.1:c.15dup
NM_001354803.1:c.189dup
NM_033507.2:c.1158dup
NM_033508.2:c.1152dup
NM_033507.3:c.1158dup
NM_033508.3:c.1152dup
NM_001354803.2:c.189dup
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Likely Pathogenic

Met criteria codes 2
PM2_Supporting PVS1

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 1.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1155dup variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 386 in NM_000162.5, adding 72 novel amino acids before encountering a stop codon (p.(Leu386AlafsTer73)). This variant, located in biologically-relevant exon 9 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 19790256). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1155dup 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.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting). gnomAD v4.0.0: absent
PVS1
This variant, located in biologically-relevant exon 9 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 19790256).
Curation History
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