NM_000162.5(GCK):c.638G>A (p.Cys213Tyr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 17, 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:: RCV003060106.3

Allele description [Variation Report for NM_000162.5(GCK):c.638G>A (p.Cys213Tyr)]

NM_000162.5(GCK):c.638G>A (p.Cys213Tyr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.638G>A (p.Cys213Tyr)

HGVS:

NC_000007.14:g.44149801C>T
NG_008847.2:g.53370G>A
NM_000162.5:c.638G>AMANE SELECT
NM_001354800.1:c.638G>A
NM_033507.3:c.641G>A
NM_033508.3:c.635G>A
NP_000153.1:p.Cys213Tyr
NP_001341729.1:p.Cys213Tyr
NP_277042.1:p.Cys214Tyr
NP_277043.1:p.Cys212Tyr
LRG_1074t1:c.638G>A
LRG_1074t2:c.641G>A
LRG_1074:g.53370G>A
LRG_1074p1:p.Cys213Tyr
LRG_1074p2:p.Cys214Tyr
NC_000007.13:g.44189400C>T

Protein change:

C212Y

Molecular consequence:

NM_000162.5:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.638G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.641G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.635G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003439951	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18248649, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439951

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 17, 2022)

germline

clinical testing

PubMed (2)
[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

Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients.

Garin I, Rica I, Estalella I, Oyarzabal M, Rodríguez-Rigual M, San Pedro JI, Pérez-Nanclares G, Fernández-Rebollo E, Busturia MA, Castaño L, Pérez de Nanclares G; Spanish MODY Group..

Clin Endocrinol (Oxf). 2008 Jun;68(6):873-8. doi: 10.1111/j.1365-2265.2008.03214.x. Epub 2008 Feb 1.

PubMed [citation]

PMID:: 18248649

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439951.2

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

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 213 of the GCK protein (p.Cys213Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with maturity onset diabetes of the young (PMID: 18248649). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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