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NM_000162.5(GCK):c.787T>C (p.Ser263Pro) AND Gestational diabetes

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 18, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000117135.10

Allele description [Variation Report for NM_000162.5(GCK):c.787T>C (p.Ser263Pro)]

NM_000162.5(GCK):c.787T>C (p.Ser263Pro)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.787T>C (p.Ser263Pro)
HGVS:
  • NC_000007.14:g.44147726A>G
  • NG_008847.2:g.55445T>C
  • NM_000162.5:c.787T>CMANE SELECT
  • NM_001354800.1:c.787T>C
  • NM_033507.3:c.790T>C
  • NM_033508.3:c.784T>C
  • NP_000153.1:p.Ser263Pro
  • NP_001341729.1:p.Ser263Pro
  • NP_277042.1:p.Ser264Pro
  • NP_277043.1:p.Ser262Pro
  • LRG_1074t1:c.787T>C
  • LRG_1074t2:c.790T>C
  • LRG_1074:g.55445T>C
  • LRG_1074p1:p.Ser263Pro
  • LRG_1074p2:p.Ser264Pro
  • NC_000007.13:g.44187325A>G
  • NM_000162.3:c.787T>C
  • NM_033508.1:c.784T>C
  • p.SER263PRO
  • p.Ser262Pro
Protein change:
S262P
Links:
dbSNP: rs193922331
NCBI 1000 Genomes Browser:
rs193922331
Molecular consequence:
  • NM_000162.5:c.787T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.787T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.790T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.784T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gestational diabetes
Synonyms:
Diabetes mellitus, gestational; Maternal diabetes
Identifiers:
MONDO: MONDO:0005406; MedGen: C0085207; Human Phenotype Ontology: HP:0009800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002072030Genetic Services Laboratory, University of Chicago
no assertion criteria provided
Likely pathogenic
(Nov 18, 2021) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002072030.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

DNA sequence analysis of the GCK gene demonstrated a sequence change, c.787T>C, in exon 7 that results in an amino acid change, p.Ser263Pro. The p.Ser263Pro change affects a poorly conserved amino acid residue located in a domain of the GCK protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ser263Pro substitution. This sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.0032% % (dbSNP rs193922331). This sequence change has been previously reported in patients with GCK-related hyperglycemia (PMIDs: 12442280, 16731834). Functional studies have also demonstrated that p.Ser263ro sequence change results in reduced protein misfolding and aberrant dimerization (PMIDs: 22820548, 16731834). These collective evidences indicate that this sequence change is the likely pathogenic.

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

Last Updated: Oct 13, 2024