NM_000162.5(GCK):c.635_637del (p.Ser212del) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Nov 13, 2023
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:: RCV000482920.5

Allele description [Variation Report for NM_000162.5(GCK):c.635_637del (p.Ser212del)]

NM_000162.5(GCK):c.635_637del (p.Ser212del)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.635_637del (p.Ser212del)

HGVS:

NC_000007.14:g.44149804_44149806del
NG_008847.2:g.53367_53369del
NM_000162.3:c.635_637del
NM_000162.5:c.635_637delMANE SELECT
NM_001354800.1:c.635_637del
NM_033507.3:c.638_640del
NM_033508.3:c.632_634del
NP_000153.1:p.Ser212del
NP_001341729.1:p.Ser212del
NP_277042.1:p.Ser213del
NP_277043.1:p.Ser211del
LRG_1074t1:c.635_637del
LRG_1074t2:c.638_640del
LRG_1074:g.53367_53369del
LRG_1074p1:p.Ser212del
LRG_1074p2:p.Ser213del
NC_000007.13:g.44189403_44189405del
NM_000162.3:c.635_637delCCT

Protein change:

S211del

Links:

dbSNP: rs193922314

NCBI 1000 Genomes Browser:

rs193922314

Molecular consequence:

NM_000162.5:c.635_637del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354800.1:c.635_637del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033507.3:c.638_640del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_033508.3:c.632_634del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568574	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 13, 2023)	germline	clinical testing	Citation Link,
SCV003839555	Genetic Services Laboratory, University of Chicago	no assertion criteria provided	Likely pathogenic (Aug 31, 2022)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568574

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Nov 13, 2023)

germline

clinical testing

Citation Link,

SCV003839555

Genetic Services Laboratory, University of Chicago

no assertion criteria provided

Likely pathogenic
(Aug 31, 2022)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000568574.5

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

Description

In-frame deletion of 1 amino acid in a non-repeat region predicted to critically alter the protein; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Identified in patients with MODY in published literature and referred for genetic testing at GeneDx in association with MODY (PMID: 29927023, 24804978); This variant is associated with the following publications: (PMID: 19790256, 27167055, 24804978, 29927023)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV003839555.1

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

Description

DNA sequence analysis of the GCK gene demonstrated a three base pair deletion in exon 6, c.635_637del. This in-frame deletion is predicted to result in the deletion of an amino acid residue, p.Ser212del. This deletion has been previously described in individuals with GCK -related MODY and neonatal hyperglycemia (PMIDs: 24804978, 29927023, 27167055 and 34374989). This sequence change has been described in the gnomAD database with a global population frequency of 0.0004% (dbSNP rs193922314). These collective evidences indicate that this sequence change is likely pathogenic, however functional studies have not been performed to prove this conclusively.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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