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NM_000162.5(GCK):c.680-2A>G AND not provided

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Jul 1, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000711782.11

Allele description [Variation Report for NM_000162.5(GCK):c.680-2A>G]

NM_000162.5(GCK):c.680-2A>G

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.680-2A>G
HGVS:
  • NC_000007.14:g.44147835T>C
  • NG_008847.2:g.55336A>G
  • NM_000162.5:c.680-2A>GMANE SELECT
  • NM_001354800.1:c.680-2A>G
  • NM_033507.3:c.683-2A>G
  • NM_033508.3:c.677-2A>G
  • LRG_1074t1:c.680-2A>G
  • LRG_1074t2:c.683-2A>G
  • LRG_1074:g.55336A>G
  • NC_000007.13:g.44187434T>C
  • NM_000162.3:c.680-2A>G
Links:
dbSNP: rs1562715657
NCBI 1000 Genomes Browser:
rs1562715657
Molecular consequence:
  • NM_000162.5:c.680-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354800.1:c.680-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_033507.3:c.683-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_033508.3:c.677-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000842179Athena Diagnostics
criteria provided, single submitter

(Athena Diagnostics Criteria)		Pathogenic
(Dec 19, 2017) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001764922GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Pathogenic
(Jul 1, 2023) 		germlineclinical testing

Citation Link,

SCV002069670Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 23, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL.

Hum Mutat. 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. Review.

PubMed [citation]
PMID:
19790256

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317
See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV000842179.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001764922.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Observed in families with MODY in published literature; however, specific patient information was not provided (Osbak et al., 2009); Not observed in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 19790256)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Genetic Services Laboratory, University of Chicago, SCV002069670.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

DNA sequence analysis of the GCK gene demonstrated a sequence change in the canonical splice acceptor site of intron 6, c.680-2A>G. This sequence change is absent from the gnomAD population database. This sequence change has been previously described in individuals with maturity-onset diabetes of the young (MODY) (PMID: 19790256). This sequence change is predicted to affects mRNA splicing and is likely to result in an absent or truncated protein. Collectively, these evidences indicate that this sequence change is pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024