NM_000162.5(GCK):c.641dup (p.Tyr214Ter) AND Maturity onset diabetes mellitus in young

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 6, 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:: RCV004017916.1

Allele description [Variation Report for NM_000162.5(GCK):c.641dup (p.Tyr214Ter)]

NM_000162.5(GCK):c.641dup (p.Tyr214Ter)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.641dup (p.Tyr214Ter)

HGVS:

NC_000007.14:g.44149798dup
NG_008847.2:g.53373dup
NM_000162.5:c.641dupMANE SELECT
NM_001354800.1:c.641dup
NM_033507.3:c.644dup
NM_033508.3:c.638dup
NP_000153.1:p.Tyr214Ter
NP_001341729.1:p.Tyr214Ter
NP_277042.1:p.Tyr215Ter
NP_277043.1:p.Tyr213Ter
LRG_1074t1:c.641dup
LRG_1074t2:c.644dup
LRG_1074:g.53373dup
LRG_1074p1:p.Tyr214Ter
LRG_1074p2:p.Tyr215Ter
NC_000007.13:g.44189397dup
NC_000007.14:g.44149797_44149798insT
NM_033507.2:c.644dupA

Protein change:

Y213*

Links:

dbSNP: rs2128821490

NCBI 1000 Genomes Browser:

rs2128821490

Molecular consequence:

NM_000162.5:c.641dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354800.1:c.641dup - nonsense - [Sequence Ontology: SO:0001587]
NM_033507.3:c.644dup - nonsense - [Sequence Ontology: SO:0001587]
NM_033508.3:c.638dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Maturity onset diabetes mellitus in young (MODY)
Synonyms:: Mason type diabetes
Identifiers:: MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848492	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Nov 6, 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

SCV004848492

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Nov 6, 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	unknown	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848492.1

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

Description

The (c.638dupA) p.Tyr213Ter variant in GCK has not been reported in individuals with maturity-onset diabetes of the young (MODY) and was absent from large population studies. This single base duplication variant leads to a premature termination codon at position 213, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the GCK gene is an established disease mechanism in maturity-onset diabetes of the young. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant MODY. ACMG/AMP Criteria applied: PVS1, PM2.

#	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: May 1, 2024

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