U.S. flag

An official website of the United States government

NM_000162.5(GCK):c.1278_1279del (p.Val427fs) AND Monogenic diabetes

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 20, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV003313229.1

Allele description [Variation Report for NM_000162.5(GCK):c.1278_1279del (p.Val427fs)]

NM_000162.5(GCK):c.1278_1279del (p.Val427fs)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.1278_1279del (p.Val427fs)
Other names:
NM_000162.5(GCK):c.1278_1279del; p.Val427fs
HGVS:
  • NC_000007.14:g.44145256_44145257del
  • NG_008847.2:g.57915_57916del
  • NM_000162.5:c.1278_1279delMANE SELECT
  • NM_001354800.1:c.1278_1279del
  • NM_001354801.1:c.267_268del
  • NM_001354802.1:c.138_139del
  • NM_001354803.2:c.312_313del
  • NM_033507.3:c.1281_1282del
  • NM_033508.3:c.1275_1276del
  • NP_000153.1:p.Val427fs
  • NP_001341729.1:p.Val427fs
  • NP_001341730.1:p.Val90fs
  • NP_001341731.1:p.Val47fs
  • NP_001341732.1:p.Val105fs
  • NP_277042.1:p.Val428fs
  • NP_277043.1:p.Val426fs
  • LRG_1074t1:c.1278_1279del
  • LRG_1074t2:c.1281_1282del
  • LRG_1074:g.57915_57916del
  • LRG_1074p1:p.Val427fs
  • LRG_1074p2:p.Val428fs
  • NC_000007.13:g.44184855_44184856del
  • NM_000162.3:c.1278_1279del
Protein change:
V105fs
Links:
dbSNP: rs2128818859
NCBI 1000 Genomes Browser:
rs2128818859
Molecular consequence:
  • NM_000162.5:c.1278_1279del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354800.1:c.1278_1279del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354801.1:c.267_268del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354802.1:c.138_139del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354803.2:c.312_313del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_033507.3:c.1281_1282del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_033508.3:c.1275_1276del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Monogenic diabetes
Identifiers:
MONDO: MONDO:0015967; MedGen: C3888631

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004012123ClinGen Monogenic Diabetes Variant Curation Expert Panel
reviewed by expert panel

(ClinGen Diabetes ACMG Specifications GCK V1.2.0)		Likely pathogenic
(Jun 20, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Monogenic Diabetes Variant Curation Expert Panel, SCV004012123.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1278_1279del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 427 (NM_000162.5), adding 31 novel amino acids before encountering a stop codon (p.(Val427AlafsTer31)). While this variant, located in exon 10 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where loss-of-function is an established disease mechanism (PVS1; PMID: 19790256). This variant is absent in gnomAD v2.1.1 (PM2_Supporting), and was identified in an individual with diabetes; however, PP4 is unable to be evaluated due to lack of clinical information (internal lab contributor). In summary, the c.1278_1279del variant meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_Supporting.

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

Last Updated: May 7, 2024