NM_000162.5(GCK):c.208G>A (p.Glu70Lys) AND Maturity-onset diabetes of the young type 2

Germline classification:: Likely pathogenic (1 submission)
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:: RCV002227431.3

Allele description [Variation Report for NM_000162.5(GCK):c.208G>A (p.Glu70Lys)]

NM_000162.5(GCK):c.208G>A (p.Glu70Lys)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.208G>A (p.Glu70Lys)

HGVS:

NC_000007.14:g.44153301C>T
NG_008847.2:g.49870G>A
NM_000162.5:c.208G>AMANE SELECT
NM_001354800.1:c.208G>A
NM_033507.3:c.211G>A
NM_033508.3:c.205G>A
NP_000153.1:p.Glu70Lys
NP_001341729.1:p.Glu70Lys
NP_277042.1:p.Glu71Lys
NP_277043.1:p.Glu69Lys
LRG_1074t1:c.208G>A
LRG_1074t2:c.211G>A
LRG_1074:g.49870G>A
LRG_1074p1:p.Glu70Lys
LRG_1074p2:p.Glu71Lys
NC_000007.13:g.44192900C>T
NM_000162.3:c.208G>A

Protein change:

E69K

Links:

dbSNP: rs2128823091

NCBI 1000 Genomes Browser:

rs2128823091

Molecular consequence:

NM_000162.5:c.208G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.208G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.211G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.205G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on RNA splicing function [Variation Ontology: 0397]

Observations:

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
SCV002506588	National Newborn Screening Laboratory, Hospital Nacional de Niños	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25741868, 17573900, 19790256

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002506588

National Newborn Screening Laboratory, Hospital Nacional de Niños

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Latin American	unknown	yes	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

Estalella I, Rica I, Perez de Nanclares G, Bilbao JR, Vazquez JA, San Pedro JI, Busturia MA, Castaño L; Spanish MODY Group..

Clin Endocrinol (Oxf). 2007 Oct;67(4):538-46. Epub 2007 Jun 15.

PubMed [citation]

PMID:: 17573900

See all PubMed Citations (3)

Details of each submission

From National Newborn Screening Laboratory, Hospital Nacional de Niños, SCV002506588.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Latin American	1	not provided	not provided	clinical testing	PubMed (3)

Description

This is a missense variant located within exon 2 and generates a change from the aminoacid Glutamic acid to Lysine in position 70. It is located in a mutational hot spot (PM1). It is not present in population databases (GnomAD exomes, GnomAD genomes) (PM2). Multiple lines of computational evidence support a deleterious effect on the gene (PP3). Missense variant in a gene that has a low rate of benign missense variation for which missense variants is a common mechanism of a disease (PP2). This variant has been reported in the literature associated with individuals with MODY2 (PMID: 17573900, 19790256)

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

Last Updated: Jun 23, 2024

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