NM_000162.5(GCK):c.565A>G (p.Ile189Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 6, 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:: RCV003479525.1

Allele description [Variation Report for NM_000162.5(GCK):c.565A>G (p.Ile189Val)]

NM_000162.5(GCK):c.565A>G (p.Ile189Val)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.565A>G (p.Ile189Val)

Other names:

NM_033508.3:c.562A>G

HGVS:

NC_000007.14:g.44149983T>C
NG_008847.2:g.53188A>G
NM_000162.5:c.565A>GMANE SELECT
NM_001354800.1:c.565A>G
NM_033507.3:c.568A>G
NM_033508.3:c.562A>G
NP_000153.1:p.Ile189Val
NP_001341729.1:p.Ile189Val
NP_277042.1:p.Ile190Val
NP_277043.1:p.Ile188Val
LRG_1074t1:c.565A>G
LRG_1074t2:c.568A>G
LRG_1074:g.53188A>G
LRG_1074p1:p.Ile189Val
LRG_1074p2:p.Ile190Val
NC_000007.13:g.44189582T>C

Protein change:

I188V

Molecular consequence:

NM_000162.5:c.565A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.565A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.568A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.562A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004223351	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33565752, 32533685 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004223351

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 6, 2023)

germline

clinical testing

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

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

The Application of Next Generation Sequencing Maturity Onset Diabetes of the Young Gene Panel in Turkish Patients from Trakya Region

Yalçıntepe S, Özgüç Çömlek F, Gürkan H, Demir S, Atlı Eİ, Atlı E, Eker D, Tütüncüler Kökenli F.

J Clin Res Pediatr Endocrinol. 2021 Aug 23;13(3):320-331. doi: 10.4274/jcrpe.galenos.2021.2020.0285. Epub 2021 Feb 10.

PubMed [citation]

PMID:: 33565752
PMCID:: PMC8388052

Genotype-Phenotype Characteristics of Turkish Children With Glucokinase Mutations Associated Maturity-Onset Diabetes of the Young.

Bolu S, Eroz R, Dogan M, Arslanoglu I, Dundar I.

Indian Pediatr. 2020 Nov 15;57(11):1037-1039. Epub 2020 Jun 12.

PubMed [citation]

PMID:: 32533685

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004223351.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: GCK c.565A>G (p.Ile189Val) results in a conservative amino acid change located in the Hexokinase, N-terminal domain (IPR022672) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251150 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.565A>G has been reported in the literature in individuals affected with Monogenic Diabetes (example, Bolu_2020, Yalntepe_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Monogenic Diabetes/Maturity Onset Diabetes Of The Young 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32533685, 33565752). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Jan 6, 2024

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