NM_000162.5(GCK):c.863+1G>A AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 29, 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:: RCV000711787.10

Allele description [Variation Report for NM_000162.5(GCK):c.863+1G>A]

NM_000162.5(GCK):c.863+1G>A

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.863+1G>A

HGVS:

NC_000007.14:g.44147649C>T
NG_008847.2:g.55522G>A
NM_000162.5:c.863+1G>AMANE SELECT
NM_001354800.1:c.863+1G>A
NM_033507.3:c.866+1G>A
NM_033508.3:c.860+1G>A
LRG_1074t1:c.863+1G>A
LRG_1074t2:c.866+1G>A
LRG_1074:g.55522G>A
NC_000007.13:g.44187248C>T
NM_000162.3:c.863+1G>A

Links:

dbSNP: rs1376796469

NCBI 1000 Genomes Browser:

rs1376796469

Molecular consequence:

NM_000162.5:c.863+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001354800.1:c.863+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_033507.3:c.866+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_033508.3:c.860+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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fabD [acyl-carrier-protein] S-malonyltransferase [Escherichia coli str. K-12 sub...
fabD [acyl-carrier-protein] S-malonyltransferase [Escherichia coli str. K-12 substr. MG1655]
Gene ID:945766

Gene
fadM long-chain acyl-CoA thioesterase FadM [Escherichia coli str. K-12 substr. M...
fadM long-chain acyl-CoA thioesterase FadM [Escherichia coli str. K-12 substr. MG1655]
Gene ID:945812

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000842184	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Oct 14, 2020)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25306193, 26467025
SCV002235594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 19790256, 21696527, 25306193, 16199547, 7553875, 9867845, 14578306, 24323243, 25015100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000842184

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Oct 14, 2020)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002235594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2022)

germline

clinical testing

PubMed (10)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL.

Hum Mutat. 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. Review.

PubMed [citation]

PMID:: 19790256

See all PubMed Citations (11)

Details of each submission

From Athena Diagnostics, SCV000842184.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235594.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

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: 585928). Disruption of this splice site has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 19790256, 21696527, 25306193). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 7 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: Sep 29, 2024

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