NM_000162.5(GCK):c.679G>A (p.Gly227Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 9, 2022
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:: RCV003060103.3

Allele description [Variation Report for NM_000162.5(GCK):c.679G>A (p.Gly227Ser)]

NM_000162.5(GCK):c.679G>A (p.Gly227Ser)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.679G>A (p.Gly227Ser)

HGVS:

NC_000007.14:g.44149760C>T
NG_008847.2:g.53411G>A
NM_000162.5:c.679G>AMANE SELECT
NM_001354800.1:c.679G>A
NM_033507.3:c.682G>A
NM_033508.3:c.676G>A
NP_000153.1:p.Gly227Ser
NP_001341729.1:p.Gly227Ser
NP_277042.1:p.Gly228Ser
NP_277043.1:p.Gly226Ser
LRG_1074t1:c.679G>A
LRG_1074t2:c.682G>A
LRG_1074:g.53411G>A
LRG_1074p1:p.Gly227Ser
LRG_1074p2:p.Gly228Ser
NC_000007.13:g.44189359C>T

Protein change:

G226S

Molecular consequence:

NM_000162.5:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.682G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.676G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

effect on RNA splicing function [Variation Ontology: 0397]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439900	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 9, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17573900, 29056535, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439900

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 9, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

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

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003439900.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense change has been observed in individual(s) with clinical features of maturity-onset diabetes of the young (PMID: 17573900, 29056535; Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 227 of the GCK protein (p.Gly227Ser). This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon.

#	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: Jun 23, 2024

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