ClinVar Genomic variation as it relates to human health
NM_000162.5(GCK):c.70C>T (p.Gln24Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000162.5(GCK):c.70C>T (p.Gln24Ter)
Variation ID: 804854 Accession: VCV000804854.7
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 7p13 7: 44153439 (GRCh38) [ NCBI UCSC ] 7: 44193038 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 19, 2020 May 1, 2024 Aug 15, 2021 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000162.5:c.70C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000153.1:p.Gln24Ter nonsense NM_001354800.1:c.70C>T NP_001341729.1:p.Gln24Ter nonsense NM_033507.3:c.73C>T NP_277042.1:p.Gln25Ter nonsense NM_033508.3:c.67C>T NP_277043.1:p.Gln23Ter nonsense NC_000007.14:g.44153439G>A NC_000007.13:g.44193038G>A NG_008847.2:g.49732C>T LRG_1074:g.49732C>T LRG_1074t1:c.70C>T LRG_1074p1:p.Gln24Ter LRG_1074t2:c.73C>T LRG_1074p2:p.Gln25Ter - Protein change
- Q25*, Q24*, Q23*
- Other names
- -
- Canonical SPDI
- NC_000007.14:44153438:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
GCK | - | - |
GRCh38 GRCh37 |
1089 | 1115 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2021 | RCV000992060.6 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 23, 2020 | RCV002363516.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Aug 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001144030.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
Comment:
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and … (more)
The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data. (less)
|
|
Pathogenic
(-)
|
criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
|
Maturity onset diabetes mellitus in young
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002605429.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet … (more)
Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1281712444 in MODY, yet. (less)
|
|
Pathogenic
(Aug 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002243828.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln24*) in the GCK gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln24*) in the GCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCK are known to be pathogenic (PMID: 7553875, 9867845, 14578306, 24323243, 25015100). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with autosomal dominant maturity-onset diabetes of the young (PMID: 19790256). ClinVar contains an entry for this variant (Variation ID: 804854). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002663115.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.Q24* pathogenic mutation (also known as c.70C>T), located in coding exon 2 of the GCK gene, results from a C to T substitution at … (more)
The p.Q24* pathogenic mutation (also known as c.70C>T), located in coding exon 2 of the GCK gene, results from a C to T substitution at nucleotide position 70. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This mutation was identified in one family with maturity-onset diabetes of the young, permanent neonatal diabetes or hyperinsulinemic hypoglycemia (Osbak KK et al. Hum. Mutat., 2009 Nov;30:1512-26). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Clinical implications of the glucokinase impaired function - GCK MODY today. | Hulín J | Physiological research | 2020 | PMID: 33129248 |
MODY2 in Asia: analysis of GCK mutations and clinical characteristics. | Zhou Y | Endocrine connections | 2020 | PMID: 32375122 |
Association of a homozygous GCK missense mutation with mild diabetes. | Marucci A | Molecular genetics & genomic medicine | 2019 | PMID: 31197960 |
Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients. | Liu L | Metabolism: clinical and experimental | 2018 | PMID: 30257192 |
Genetic and clinical characteristics of Chinese children with Glucokinase-maturity-onset diabetes of the young (GCK-MODY). | Li X | BMC pediatrics | 2018 | PMID: 29510678 |
GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature. | Ping Xiao Y | Journal of pediatric endocrinology & metabolism : JPEM | 2016 | PMID: 27269892 |
Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability. | Raimondo A | Human molecular genetics | 2014 | PMID: 25015100 |
De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. | Stanik J | Diabetologia | 2014 | PMID: 24323243 |
Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. | Osbak KK | Human mutation | 2009 | PMID: 19790256 |
Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway. | Njølstad PR | Diabetes | 2003 | PMID: 14578306 |
Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. | Postic C | The Journal of biological chemistry | 1999 | PMID: 9867845 |
Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. | Grupe A | Cell | 1995 | PMID: 7553875 |
click to load more click to collapse |
Text-mined citations for rs1281712444 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.