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]
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  • No ClinVar Id was directly found from the curated document

Variant: NM_001354803.2:c.295G>T

CA367397285

Gene: GCK
Condition: maturity-onset diabetes of the young type 2
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: f537eef7-9704-4f2f-be53-fc6f5e648353

HGVS expressions

NM_001354803.2:c.295G>T
NC_000007.14:g.44145273C>A
CM000669.2:g.44145273C>A
NC_000007.13:g.44184872C>A
CM000669.1:g.44184872C>A
NC_000007.12:g.44151397C>A
NG_008847.1:g.49151G>T
NG_008847.2:g.57898G>T
ENST00000395796.8:c.*1259G>T
ENST00000616242.5:c.*381G>T
ENST00000683378.1:n.487G>T
ENST00000336642.9:c.295G>T
ENST00000345378.7:c.1264G>T
ENST00000403799.8:c.1261G>T
ENST00000671824.1:c.1324G>T
ENST00000672743.1:n.273G>T
ENST00000673284.1:c.1261G>T
ENST00000336642.8:n.313G>T
ENST00000345378.6:c.1264G>T
ENST00000395796.7:c.1258G>T
ENST00000403799.7:c.1261G>T
ENST00000437084.1:c.1210G>T
ENST00000459642.1:n.641G>T
ENST00000616242.4:n.1258G>T
NM_000162.3:c.1261G>T
NM_033507.1:c.1264G>T
NM_033508.1:c.1258G>T
NM_000162.4:c.1261G>T
NM_001354800.1:c.1261G>T
NM_001354801.1:c.250G>T
NM_001354802.1:c.121G>T
NM_001354803.1:c.295G>T
NM_033507.2:c.1264G>T
NM_033508.2:c.1258G>T
NM_000162.5:c.1261G>T
NM_033507.3:c.1264G>T
NM_033508.3:c.1258G>T

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PP4
Not Met criteria codes 2
PS4 PP1

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 1.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1261G>T variant in the glucokinase gene, GCK, results in a premature termination at codon 421 (p.(Glu421Ter)) of NM_000162.5. While this variant, located in exon 10 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where loss-of-function is an established disease mechanism (PVS1). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and fasting glucose between 5.5-8 mmol/L) (PP4; internal lab contributors). In summary, c.1261G>T meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_supporting, PP4.
Met criteria codes
PM2_Supporting
This variant is absent in gnomAD v2.1.1 (PM2_Supporting).
PVS1
While this variant, located in exon 10 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where loss-of-function is an established disease mechanism (PVS1).
PP4
This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and fasting glucose between 5.5-8 mmol/L) (PP4; internal lab contributors).
Not Met criteria codes
PS4
1 case from Exeter database
PP1
1 meiosis in 1 family
Approved on: 2023-06-25
Published on: 2023-06-25
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