NM_000162.5(GCK):c.1324G>A (p.Glu442Lys) AND Permanent neonatal diabetes mellitus

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 5, 2022
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:: RCV001824153.3

Allele description [Variation Report for NM_000162.5(GCK):c.1324G>A (p.Glu442Lys)]

NM_000162.5(GCK):c.1324G>A (p.Glu442Lys)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1324G>A (p.Glu442Lys)

HGVS:

NC_000007.14:g.44145210C>T
NG_008847.2:g.57961G>A
NM_000162.5:c.1324G>AMANE SELECT
NM_001354800.1:c.1324G>A
NM_001354801.1:c.313G>A
NM_001354802.1:c.184G>A
NM_001354803.2:c.358G>A
NM_033507.3:c.1327G>A
NM_033508.3:c.1321G>A
NP_000153.1:p.Glu442Lys
NP_001341729.1:p.Glu442Lys
NP_001341730.1:p.Glu105Lys
NP_001341731.1:p.Glu62Lys
NP_001341732.1:p.Glu120Lys
NP_277042.1:p.Glu443Lys
NP_277043.1:p.Glu441Lys
LRG_1074t1:c.1324G>A
LRG_1074t2:c.1327G>A
LRG_1074:g.57961G>A
LRG_1074p1:p.Glu442Lys
LRG_1074p2:p.Glu443Lys
NC_000007.13:g.44184809C>T
NM_000162.3:c.1324G>A

Protein change:

E105K

Links:

dbSNP: rs758737171

NCBI 1000 Genomes Browser:

rs758737171

Molecular consequence:

NM_000162.5:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1324G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.184G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.358G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1327G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1321G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Permanent neonatal diabetes mellitus (PNDM)
Synonyms:: Permanent diabetes mellitus of infancy
Identifiers:: MONDO: MONDO:0100164; MedGen: C1833104; OMIM: PS606176

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073765	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28247534, 27188453, 19884385, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002073765

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 5, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization.

Martínez R, Gutierrez-Nogués Á, Fernández-Ramos C, Velayos T, Vela A; Spanish Congenital Hyperinsulinism Group., Navas MÁ, Castaño L.

Clin Endocrinol (Oxf). 2017 Jun;86(6):778-783. doi: 10.1111/cen.13318. Epub 2017 Mar 27.

PubMed [citation]

PMID:: 28247534

Clinical and genetic characterization of congenital hyperinsulinism in Spain.

Martínez R, Fernández-Ramos C, Vela A, Velayos T, Aguayo A, Urrutia I, Rica I, Castaño L; Spanish Congenital Hyperinsulinism Group..

Eur J Endocrinol. 2016 Jun;174(6):717-26. doi: 10.1530/EJE-16-0027.

PubMed [citation]

PMID:: 27188453

See all PubMed Citations (4)

Details of each submission

From DASA, SCV002073765.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The c.1324G>A;p.(Glu442Lys) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 28247534; 27188453; 19884385) - PS4. The variant is present at low allele frequencies population databases (rs758737171 – gnomAD 0.0001314%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The variant co-segregated with disease in multiple affected family members (PP1: 19884385) - PP1. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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