NM_000162.5(GCK):c.686del (p.Gly229fs) AND Maturity-onset diabetes of the young type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 10, 2024
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:: RCV003987576.1

Allele description [Variation Report for NM_000162.5(GCK):c.686del (p.Gly229fs)]

NM_000162.5(GCK):c.686del (p.Gly229fs)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.686del (p.Gly229fs)

HGVS:

NC_000007.14:g.44147829del
NG_008847.2:g.55344del
NM_000162.5:c.686delMANE SELECT
NM_001354800.1:c.686del
NM_033507.3:c.689del
NM_033508.3:c.683del
NP_000153.1:p.Gly229fs
NP_001341729.1:p.Gly229fs
NP_277042.1:p.Gly230fs
NP_277043.1:p.Gly228fs
LRG_1074t1:c.686del
LRG_1074t2:c.689del
LRG_1074:g.55344del
LRG_1074p1:p.Gly229fs
LRG_1074p2:p.Gly230fs
NC_000007.13:g.44187428del
NM_000162.5:c.686delGMANE SELECT

Protein change:

G228fs

Links:

dbSNP: rs1554335164

NCBI 1000 Genomes Browser:

rs1554335164

Molecular consequence:

NM_000162.5:c.686del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354800.1:c.686del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033507.3:c.689del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033508.3:c.683del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Maturity-onset diabetes of the young type 2
Synonyms:: MODY type 2; Diabetes mellitus MODY type 2; MODY glucokinase-related; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007453; MedGen: C0342277; Orphanet: 552; OMIM: 125851

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004804346	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 10, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004804346

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 10, 2024)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations.

Aykut A, Karaca E, Onay H, Gökşen D, Çetinkalp Ş, Eren E, Ersoy B, Çakır EP, Büyükinan M, Kara C, Anık A, Kırel B, Özen S, Atik T, Darcan Ş, Özkınay F.

Gene. 2018 Jan 30;641:186-189. doi: 10.1016/j.gene.2017.10.057. Epub 2017 Oct 19.

PubMed [citation]

PMID:: 29056535

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004804346.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: GCK c.686delG (p.Gly229AlafsX65) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250196 control chromosomes (gnomAD). c.686delG has been reported in the literature in at least one individual affected with Maturity Onset Diabetes Of The Young 2 (e.g., Aykut_2018). These data suggest the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 29056535). ClinVar contains an entry for this variant (Variation ID: 447414). Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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