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NM_000162.5(GCK):c.579+1G>A AND Maturity onset diabetes mellitus in young

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 20, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002359763.2

Allele description [Variation Report for NM_000162.5(GCK):c.579+1G>A]

NM_000162.5(GCK):c.579+1G>A

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.579+1G>A
HGVS:
  • NC_000007.14:g.44149968C>T
  • NG_008847.2:g.53203G>A
  • NM_000162.5:c.579+1G>AMANE SELECT
  • NM_001354800.1:c.579+1G>A
  • NM_033507.3:c.582+1G>A
  • NM_033508.3:c.576+1G>A
  • LRG_1074t1:c.579+1G>A
  • LRG_1074t2:c.582+1G>A
  • LRG_1074:g.53203G>A
  • NC_000007.13:g.44189567C>T
  • NM_000162.3:c.579+1G>A
Molecular consequence:
  • NM_000162.5:c.579+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354800.1:c.579+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_033507.3:c.582+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_033508.3:c.576+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Maturity onset diabetes mellitus in young (MODY)
Synonyms:
Mason type diabetes
Identifiers:
MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002651946Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 20, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

From clinicogenetic studies of maturity-onset diabetes of the young to unraveling complex mechanisms of glucokinase regulation.

Sagen JV, Odili S, Bjørkhaug L, Zelent D, Buettger C, Kwagh J, Stanley C, Dahl-Jørgensen K, de Beaufort C, Bell GI, Han Y, Grimsby J, Taub R, Molven A, Søvik O, Njølstad PR, Matschinsky FM.

Diabetes. 2006 Jun;55(6):1713-22.

PubMed [citation]
PMID:
16731834

Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations.

Pruhova S, Dusatkova P, Sumnik Z, Kolouskova S, Pedersen O, Hansen T, Cinek O, Lebl J.

Pediatr Diabetes. 2010 Dec;11(8):529-35. doi: 10.1111/j.1399-5448.2010.00646.x.

PubMed [citation]
PMID:
20337973

Details of each submission

From Ambry Genetics, SCV002651946.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.579+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 5 of the GCK gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown; however, the impacted region is critical for protein function and a significant portion of the protein is affected (Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. Two alterations at the same nucleotide position, c.579+1G>C and c.579+1G>T, have been described in individuals and families with a maturity-onset diabetes of the young (MODY) phenotype (Sagen JV et al. Diabetes, 2006 Jun;55:1713-22; Pruhova S et al. Pediatr Diabetes, 2010 Dec;11:529-35). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 7, 2024