The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document


Variant: NM_001354803.2:c.432A>G

CA367396716

Gene: GCK
Condition: monogenic diabetes
Inheritance Mode: Semidominant inheritance
UUID: 4af7b7e3-ee4b-420c-88ad-d85afd2036fd
Approved on: 2023-08-10
Published on: 2023-08-10

HGVS expressions

NM_001354803.2:c.432A>G
NC_000007.14:g.44145136T>C
CM000669.2:g.44145136T>C
NC_000007.13:g.44184735T>C
CM000669.1:g.44184735T>C
NC_000007.12:g.44151260T>C
NG_008847.1:g.49288A>G
NG_008847.2:g.58035A>G
ENST00000395796.8:c.*1396A>G
ENST00000616242.5:c.*518A>G
ENST00000683378.1:n.624A>G
ENST00000336642.9:c.432A>G
ENST00000345378.7:c.1401A>G
ENST00000403799.8:c.1398A>G
ENST00000671824.1:c.1461A>G
ENST00000672743.1:n.381+29A>G
ENST00000673284.1:c.1369+29A>G
ENST00000336642.8:n.450A>G
ENST00000345378.6:c.1401A>G
ENST00000395796.7:c.1395A>G
ENST00000403799.7:c.1398A>G
ENST00000437084.1:c.1347A>G
ENST00000459642.1:n.778A>G
ENST00000616242.4:n.1395A>G
NM_000162.3:c.1398A>G
NM_033507.1:c.1401A>G
NM_033508.1:c.1395A>G
NM_000162.4:c.1398A>G
NM_001354800.1:c.1369+29A>G
NM_001354801.1:c.387A>G
NM_001354802.1:c.229+29A>G
NM_001354803.1:c.432A>G
NM_033507.2:c.1401A>G
NM_033508.2:c.1395A>G
NM_000162.5:c.1398A>G
NM_033507.3:c.1401A>G
NM_033508.3:c.1395A>G

Likely Pathogenic

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

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.1398A>G variant in the glucokinase gene, GCK, causes an amino acid change at the stop codon of the final exon (10/10), resulting in the addition of 144 amino acids at the end of the protein (p.(Ter466ArgextTer144)). This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history consistent with GCK-hyperglycemia, but there was insufficient clinical data to evaluate for PP4 (internal lab contributors). Taken together, this evidence supports the classification of this variant as likely pathogenic for GCK-MODY. ACMG/AMP criteria applied, as specified by the ClinGen MDEP: PVS1, PM2_Supporting. (Specification version 1.2.0, approved 6/7/23)
Met criteria codes
PM2_Supporting
Absent in gnomAD
PVS1
This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256).
Not Met criteria codes
PS4
Seen in one individual (internal lab contributors)
PP4
This variant was identified in an individual with a clinical history consistent with GCK-hyperglycemia, but there was insufficient clinical data to evaluate for PP4 (internal lab contributors).
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.
¤ Powered by BCM's Genboree.