NM_000162.5(GCK):c.660C>A (p.Cys220Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 5, 2023
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:: RCV001658238.8

Allele description

NM_000162.5(GCK):c.660C>A (p.Cys220Ter)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.660C>A (p.Cys220Ter)

Other names:

NM_000162.5(GCK):c.660C>A; p.Cys220Ter

HGVS:

NC_000007.14:g.44149779G>T
NG_008847.2:g.53392C>A
NM_000162.5:c.660C>AMANE SELECT
NM_001354800.1:c.660C>A
NM_033507.3:c.663C>A
NM_033508.3:c.657C>A
NP_000153.1:p.Cys220Ter
NP_001341729.1:p.Cys220Ter
NP_277042.1:p.Cys221Ter
NP_277043.1:p.Cys219Ter
LRG_1074t1:c.660C>A
LRG_1074t2:c.663C>A
LRG_1074:g.53392C>A
LRG_1074p1:p.Cys220Ter
LRG_1074p2:p.Cys221Ter
NC_000007.13:g.44189378G>T
NC_000007.13:g.44189378G>T
NM_000162.3:c.660C>A

Protein change:

C219*

Links:

dbSNP: rs142952813

NCBI 1000 Genomes Browser:

rs142952813

Molecular consequence:

NM_000162.5:c.660C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354800.1:c.660C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033507.3:c.663C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033508.3:c.657C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001880736	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Sep 5, 2023)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 33477506, 31638168, 11942313, 16602010, 26467025
SCV002567552	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 17, 2022)	germline	clinical testing	Citation Link,
SCV004295170	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 11942313, 26641800, 31638168, 33852230, 7553875, 9867845, 14578306, 24323243, 25015100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001880736

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Sep 5, 2023)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002567552

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 17, 2022)

germline

clinical testing

Citation Link,

SCV004295170

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 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	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients.

Ivanoshchuk DE, Shakhtshneider EV, Rymar OD, Ovsyannikova AK, Mikhailova SV, Fishman VS, Valeev ES, Orlov PS, Voevoda MI.

J Pers Med. 2021 Jan 18;11(1). doi:pii: 57. 10.3390/jpm11010057.

PubMed [citation]

PMID:: 33477506
PMCID:: PMC7831070

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

Feigerlová E, Pruhová S, Dittertová L, Lebl J, Pinterová D, Kolostová K, Cerná M, Pedersen O, Hansen T.

Eur J Pediatr. 2006 Jul;165(7):446-52. Epub 2006 Apr 7.

PubMed [citation]

PMID:: 16602010

See all PubMed Citations (13)

Details of each submission

From Athena Diagnostics, SCV001880736.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is expected to result in the loss of a functional protein. This variant has been identified in multiple unrelated individuals with clinical features of MODY. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).

#	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 GeneDx, SCV002567552.2

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33852230, 26641800, 25525159, 11942313, 31638168, 20337973, 26552609)

#	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 Invitae, SCV004295170.1

#	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. ClinVar contains an entry for this variant (Variation ID: 1172896). This premature translational stop signal has been observed in individual(s) with clinical features of GCK-related conditions (PMID: 11942313, 26641800, 31638168, 33852230). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys220*) 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 16, 2024

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