NM_000162.5(GCK):c.484-2A>G AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 11, 2023
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:: RCV003698896.1

Allele description [Variation Report for NM_000162.5(GCK):c.484-2A>G]

NM_000162.5(GCK):c.484-2A>G

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.484-2A>G

HGVS:

NC_000007.14:g.44150066T>C
NG_008847.2:g.53105A>G
NM_000162.5:c.484-2A>GMANE SELECT
NM_001354800.1:c.484-2A>G
NM_033507.3:c.487-2A>G
NM_033508.3:c.481-2A>G
LRG_1074t1:c.484-2A>G
LRG_1074t2:c.487-2A>G
LRG_1074:g.53105A>G
NC_000007.13:g.44189665T>C

Molecular consequence:

NM_000162.5:c.484-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354800.1:c.484-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_033507.3:c.487-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_033508.3:c.481-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Natriuretic Peptide, Brain
Natriuretic Peptide, Brain
A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits se...<br/>Year introduced: 1999, use BRAIN NATRIURETIC PEPTIDE (NM) 1988-1998

MeSH
D020097 (1)
MeSH
LOC106755768 [Vigna radiata]
LOC106755768 [Vigna radiata]
Gene ID:106755768

Gene
Meglutol
Meglutol
An antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids. It acts by interfering with the enzymatic steps involved in the conver...<br/>Year introduced: 1996

MeSH
Homologene neighbors for GEO Profiles (Select 115429055) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004467476	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 11, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 23771925, 16199547, 7553875, 9867845, 14578306, 24323243, 25015100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004467476

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 11, 2023)

germline

clinical testing

PubMed (8)
[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

Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth.

Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, Dolan LM, Greenbaum CJ, Imperatore G, Lawrence JM, Marcovina SM, Mayer-Davis E, Rodriguez BL, Steck AK, Williams DE, Hattersley AT; SEARCH for Diabetes in Youth Study Group..

J Clin Endocrinol Metab. 2013 Oct;98(10):4055-62. doi: 10.1210/jc.2013-1279. Epub 2013 Jun 14.

PubMed [citation]

PMID:: 23771925
PMCID:: PMC3790621

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV004467476.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1700680). Disruption of this splice site has been observed in individuals with clinical features of maturity onset diabetes of the young (PMID: 23771925; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 4 of the GCK gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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: Feb 28, 2024

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