NM_000162.5(GCK):c.775G>A (p.Ala259Thr) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jun 23, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001562849.11

Allele description [Variation Report for NM_000162.5(GCK):c.775G>A (p.Ala259Thr)]

NM_000162.5(GCK):c.775G>A (p.Ala259Thr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.775G>A (p.Ala259Thr)

Other names:

NM_000162.5(GCK):c.775G>A; p.Ala259Thr

HGVS:

NC_000007.14:g.44147738C>T
NG_008847.2:g.55433G>A
NM_000162.5:c.775G>AMANE SELECT
NM_001354800.1:c.775G>A
NM_033507.3:c.778G>A
NM_033508.3:c.772G>A
NP_000153.1:p.Ala259Thr
NP_001341729.1:p.Ala259Thr
NP_277042.1:p.Ala260Thr
NP_277043.1:p.Ala258Thr
LRG_1074t1:c.775G>A
LRG_1074t2:c.778G>A
LRG_1074:g.55433G>A
LRG_1074p1:p.Ala259Thr
LRG_1074p2:p.Ala260Thr
NC_000007.13:g.44187337C>T
NM_000162.3:c.775G>A

Protein change:

A258T

Links:

dbSNP: rs1375656631

NCBI 1000 Genomes Browser:

rs1375656631

Molecular consequence:

NM_000162.5:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.775G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.778G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.772G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

828718[uid] AND (alive[prop]) (1)
Gene
Ankyrin repeat family protein / BTB/POZ domain-containing protein [Arabidopsis ...
Ankyrin repeat family protein / BTB/POZ domain-containing protein [Arabidopsis thaliana]
Gene ID:828718

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001785683	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 23, 2022)	germline	clinical testing	Citation Link,
SCV002176700	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 25, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9713013, 22761713, 25414397, 26287533, 31638168, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001785683

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 23, 2022)

germline

clinical testing

Citation Link,

SCV002176700

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 25, 2022)

germline

clinical testing

PubMed (6)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic testing for maturity onset diabetes of the young in childhood hyperglycaemia.

Matyka KA, Beards F, Appleton M, Ellard S, Hattersley A, Dunger DB.

Arch Dis Child. 1998 Jun;78(6):552-4.

PubMed [citation]

PMID:: 9713013
PMCID:: PMC1717591

Glucokinase (GCK) mutations and their characterization in MODY2 children of southern Italy.

Capuano M, Garcia-Herrero CM, Tinto N, Carluccio C, Capobianco V, Coto I, Cola A, Iafusco D, Franzese A, Zagari A, Navas MA, Sacchetti L.

PLoS One. 2012;7(6):e38906. doi: 10.1371/journal.pone.0038906. Epub 2012 Jun 20.

PubMed [citation]

PMID:: 22761713
PMCID:: PMC3385652

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV001785683.3

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

Description

Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 14517956, 25414397, 18271687, 34956103, 29056535, 26875109, 31604004, 9662401, 26287533, 29927023, 9713013, 22761713, 31638168, Sangwoo-2022[Article], 34101350, 35029855)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002176700.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 435302). This missense change has been observed in individuals with clinical features of autosomal dominant maturity onset diabetes of the young (PMID: 9713013, 22761713, 25414397, 26287533, 31638168; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 259 of the GCK protein (p.Ala259Thr).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine