NM_000162.5(GCK):c.771G>A (p.Trp257Ter) AND Monogenic diabetes

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 13, 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:: RCV002509759.1

Allele description [Variation Report for NM_000162.5(GCK):c.771G>A (p.Trp257Ter)]

NM_000162.5(GCK):c.771G>A (p.Trp257Ter)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.771G>A (p.Trp257Ter)

HGVS:

NC_000007.14:g.44147742C>T
NG_008847.2:g.55429G>A
NM_000162.5:c.771G>AMANE SELECT
NM_001354800.1:c.771G>A
NM_033507.3:c.774G>A
NM_033508.3:c.768G>A
NP_000153.1:p.Trp257Ter
NP_001341729.1:p.Trp257Ter
NP_277042.1:p.Trp258Ter
NP_277043.1:p.Trp256Ter
LRG_1074t1:c.771G>A
LRG_1074t2:c.774G>A
LRG_1074:g.55429G>A
LRG_1074p1:p.Trp257Ter
LRG_1074p2:p.Trp258Ter
NC_000007.13:g.44187341C>T
NM_000162.3:c.771G>A

Protein change:

W256*

Links:

dbSNP: rs2128820597

NCBI 1000 Genomes Browser:

rs2128820597

Molecular consequence:

NM_000162.5:c.771G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354800.1:c.771G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033507.3:c.774G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033508.3:c.768G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Monogenic diabetes
Identifiers:: MONDO: MONDO:0015967; MedGen: C3888631

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CBR NADH:cytochrome B5 reductase 1 [Arabidopsis thaliana]
CBR NADH:cytochrome B5 reductase 1 [Arabidopsis thaliana]
Gene ID:831645

Gene
831645[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002819506	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Dec 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30592380, 32375122, 33477506 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002819506

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Dec 13, 2022)

germline

clinical testing

PubMed (3)
[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

Identification and functional analysis of GCK gene mutations in 12 Chinese families with hyperglycemia.

Wang Z, Diao C, Liu Y, Li M, Zheng J, Zhang Q, Yu M, Zhang H, Ping F, Li M, Xiao X.

J Diabetes Investig. 2019 Jul;10(4):963-971. doi: 10.1111/jdi.13001. Epub 2019 Feb 1.

PubMed [citation]

PMID:: 30592380
PMCID:: PMC6626954

MODY2 in Asia: analysis of GCK mutations and clinical characteristics.

Zhou Y, Wang S, Wu J, Dong J, Liao L.

Endocr Connect. 2020 May;9(5):471-478. doi: 10.1530/EC-20-0074.

PubMed [citation]

PMID:: 32375122
PMCID:: PMC7274558

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819506.1

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

Description

Variant summary: GCK c.771G>A (p.Trp257X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251090 control chromosomes (gnomAD). c.771G>A has been reported in the literature in individuals affected with Diabetes, MODY2 (Wang_2018, Zhou_2020, Ivanoshchuk_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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: Sep 29, 2024

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