NM_000162.5(GCK):c.835G>A (p.Glu279Lys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 30, 2020
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:: RCV001817969.4

Allele description [Variation Report for NM_000162.5(GCK):c.835G>A (p.Glu279Lys)]

NM_000162.5(GCK):c.835G>A (p.Glu279Lys)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.835G>A (p.Glu279Lys)

HGVS:

NC_000007.14:g.44147678C>T
NG_008847.2:g.55493G>A
NM_000162.5:c.835G>AMANE SELECT
NM_001354800.1:c.835G>A
NM_033507.3:c.838G>A
NM_033508.3:c.832G>A
NP_000153.1:p.Glu279Lys
NP_001341729.1:p.Glu279Lys
NP_277042.1:p.Glu280Lys
NP_277043.1:p.Glu278Lys
LRG_1074t1:c.835G>A
LRG_1074t2:c.838G>A
LRG_1074:g.55493G>A
LRG_1074p1:p.Glu279Lys
LRG_1074p2:p.Glu280Lys
NC_000007.13:g.44187277C>T

Protein change:

E278K

Links:

dbSNP: rs104894005

NCBI 1000 Genomes Browser:

rs104894005

Molecular consequence:

NM_000162.5:c.835G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.835G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.832G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002067511	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 30, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002067511

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 30, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002067511.1

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

Description

DNA sequence analysis of the GCK gene demonstrated a sequence change, c.835G>A, in exon 7 that results in an amino acid change, p.Glu279Lys. This sequence change does not appear to have been previously described in patients with GCK-related disorders and has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.0032% (dbSNP rs104894005). The p.Glu279Lys change affects a highly conserved amino acid residue located in a hexokinase C-terminal domain of the GCK protein that is known to be functional. The p.Glu279Lys substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Glu279Lys change remains unknown at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine