NM_000162.5(GCK):c.1312_1314del (p.Phe438del) AND Monogenic diabetes

Germline classification:: Uncertain significance (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:: RCV003313353.1

Allele description [Variation Report for NM_000162.5(GCK):c.1312_1314del (p.Phe438del)]

NM_000162.5(GCK):c.1312_1314del (p.Phe438del)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1312_1314del (p.Phe438del)

Other names:

NM_001354803.2:c.346_348del

HGVS:

NC_000007.14:g.44145221_44145223del
NG_008847.2:g.57949_57951del
NM_000162.5:c.1312_1314delMANE SELECT
NM_001354800.1:c.1312_1314del
NM_001354801.1:c.301_303del
NM_001354802.1:c.172_174del
NM_001354803.2:c.346_348del
NM_033507.3:c.1315_1317del
NM_033508.3:c.1309_1311del
NP_000153.1:p.Phe438del
NP_001341729.1:p.Phe438del
NP_001341730.1:p.Phe101del
NP_001341731.1:p.Phe58del
NP_001341732.1:p.Phe116del
NP_277042.1:p.Phe439del
NP_277043.1:p.Phe437del
LRG_1074t1:c.1312_1314del
LRG_1074t2:c.1315_1317del
LRG_1074:g.57949_57951del
LRG_1074p1:p.Phe438del
LRG_1074p2:p.Phe439del
NC_000007.13:g.44184820_44184822del

Protein change:

F101del

Molecular consequence:

NM_000162.5:c.1312_1314del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354800.1:c.1312_1314del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354801.1:c.301_303del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354802.1:c.172_174del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354803.2:c.346_348del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033507.3:c.1315_1317del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033508.3:c.1309_1311del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004012119	ClinGen Monogenic Diabetes Variant Curation Expert Panel	reviewed by expert panel (ClinGen Diabetes ACMG Specifications GCK V1.2.0)	Uncertain significance (Jun 20, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004012119

ClinGen Monogenic Diabetes Variant Curation Expert Panel

reviewed by expert panel

(ClinGen Diabetes ACMG Specifications GCK V1.2.0)

Uncertain significance
(Jun 20, 2023)

germline

curation

Citation Link

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	curation

Details of each submission

From ClinGen Monogenic Diabetes Variant Curation Expert Panel, SCV004012119.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.1312_1314del variant in the glucokinase gene, GCK, is a three base pair deletion resulting in the in-frame deletion of one amino acid codon 438 (p.(Phe438del)) within exon 10 of NM_000162.5. The c.1312_1314del variant is predicted to change the length of the protein due an in-frame deletion of a single amino acid in a nonrepeat region (PM4_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting), and was identified in an individual with a clinical history suggestive of GCK-MODY; however, PP4 could not be evaluated due to insufficient clinical information (internal lab contributor). In summary, the c.1312_1314del variant meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PM2_Supporting, PM4_Supporting.

#	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: Jul 22, 2023

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