NM_000162.5(GCK):c.468del (p.His156fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 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:: RCV002616917.3

Allele description [Variation Report for NM_000162.5(GCK):c.468del (p.His156fs)]

NM_000162.5(GCK):c.468del (p.His156fs)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.468del (p.His156fs)

HGVS:

NC_000007.14:g.44150971del
NG_008847.2:g.52200del
NM_000162.5:c.468delMANE SELECT
NM_001354800.1:c.468del
NM_033507.3:c.471del
NM_033508.3:c.465del
NP_000153.1:p.His156fs
NP_001341729.1:p.His156fs
NP_277042.1:p.His157fs
NP_277043.1:p.His155fs
LRG_1074t1:c.468del
LRG_1074t2:c.471del
LRG_1074:g.52200del
LRG_1074p1:p.His156fs
LRG_1074p2:p.His157fs
NC_000007.13:g.44190570del

Protein change:

H155fs

Molecular consequence:

NM_000162.5:c.468del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354800.1:c.468del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033507.3:c.471del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033508.3:c.465del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002953247	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 30977832, 7553875, 9867845, 14578306, 24323243, 25015100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002953247

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2022)

germline

clinical testing

PubMed (7)
[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

Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population.

Park SS, Jang SS, Ahn CH, Kim JH, Jung HS, Cho YM, Lee YA, Shin CH, Chae JH, Kim JH, Choi SH, Jang HC, Bae JC, Won JC, Kim SH, Kim JI, Kwak SH, Park KS.

J Clin Endocrinol Metab. 2019 Sep 1;104(9):4188-4198. doi: 10.1210/jc.2018-02397.

PubMed [citation]

PMID:: 30977832

Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis.

Grupe A, Hultgren B, Ryan A, Ma YH, Bauer M, Stewart TA.

Cell. 1995 Oct 6;83(1):69-78.

PubMed [citation]

PMID:: 7553875

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002953247.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This premature translational stop signal has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 30977832). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His156Glnfs*48) in the GCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCK are known to be pathogenic (PMID: 7553875, 9867845, 14578306, 24323243, 25015100).

#	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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