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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004848492Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Nov 6, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024