NM_000402.4(G6PD):c.653C>T (p.Ser218Phe) AND not provided

Germline classification:: Pathogenic (13 submissions)
Last evaluated:: Aug 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000079409.63

Allele description [Variation Report for NM_000402.4(G6PD):c.653C>T (p.Ser218Phe)]

NM_000402.4(G6PD):c.653C>T (p.Ser218Phe)

Gene:

G6PD:glucose-6-phosphate dehydrogenase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000402.4(G6PD):c.653C>T (p.Ser218Phe)

Other names:

G6PD, SER188PHE; G6PD Birmingham; G6PD Cagliari; G6PD Dallas; G6PD Mediterranean; G6PD Panama; G6PD Sassari

HGVS:

NC_000023.11:g.154534419G>A
NG_009015.2:g.18154C>T
NM_000402.4:c.653C>T
NM_001042351.3:c.563C>T
NM_001360016.2:c.563C>TMANE SELECT
NP_000393.4:p.Ser218Phe
NP_001035810.1:p.Ser188Phe
NP_001035810.1:p.Ser188Phe
NP_001035810.1:p.Ser188Phe
NP_001346945.1:p.Ser188Phe
NC_000023.10:g.153762634G>A
NM_000402.3:c.653C>T
NM_001042351.1:c.563C>T
NM_001042351.2:c.563C>T
NM_001042351.2:c.[563C>T]
NM_001042351.3:c.563C>T
NM_001360016.2:c.563C>T

Protein change:

S188F; SER188PHE

Links:

Genetic Testing Registry (GTR): GTR000613302; OMIM: 305900.0006; dbSNP: rs5030868

NCBI 1000 Genomes Browser:

rs5030868

Molecular consequence:

NM_000402.4:c.653C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042351.3:c.563C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001360016.2:c.563C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

198

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Protein CBR-SYG-1 [Caenorhabditis briggsae]
Protein CBR-SYG-1 [Caenorhabditis briggsae]
gi|2158433601|ref|XP_045092028.1|

Protein
crustin 2 [Procambarus clarkii]
crustin 2 [Procambarus clarkii]
gi|328899144|gb|AEB54630.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000231598	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (May 15, 2017)	germline	clinical testing	Citation Link,
SCV000321681	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 5, 2022)	germline	clinical testing	Citation Link,
SCV000885494	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Pathogenic (Nov 3, 2023)	germline	clinical testing	Citation Link,
SCV001150542	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV001447745	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001741952	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001807662	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001928877	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001976349	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002818285	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004024683	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225543	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 8, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1978555, 22293322, 24586352, 3393536, 25741868
SCV005197994	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 29, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	144	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	54	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East.

Kurdi-Haidar B, Mason PJ, Berrebi A, Ankra-Badu G, al-Ali A, Oppenheim A, Luzzatto L.

Am J Hum Genet. 1990 Dec;47(6):1013-9.

PubMed [citation]

PMID:: 1978555
PMCID:: PMC1683892

Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations.

Minucci A, Moradkhani K, Hwang MJ, Zuppi C, Giardina B, Capoluongo E.

Blood Cells Mol Dis. 2012 Mar 15;48(3):154-65. doi: 10.1016/j.bcmd.2012.01.001. Epub 2012 Jan 30.

PubMed [citation]

PMID:: 22293322

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000231598.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	45	not provided	not provided	clinical testing	not provided

#	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		45	not provided	not provided	not provided

From GeneDx, SCV000321681.10

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

Description

Published functional studies demonstrate decreased enzyme activity in circulating erythrocytes, increased affinity for G6P, and decreased in vitro thermostability (Vulliamy et al., 1998); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23479361, 27535533, 31152693, 33413378, 31322791, 24460025, 3393536, 27884173, 19594365, 24586352, 1978555, 25548459, 28492530, 8611726, 28492532, 27853304, 27108201, 30097005, 31863082, 33069889, 31019026, 31980526, 34272389, 34426522, 33072997, 33083013, 30755392, 12215013, 32535712, 32860008, 33726816, 1978554, 22906047)

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885494.9

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

Description

The G6PD c.563C>T; p.Ser188Phe variant (rs5030868), also known as G6PD Mediterranean, is reported in the literature in multiple individuals affected with hemolytic anemia, hyperbilirubinemia and G6PD deficiency (Hellani 2009, Jamornthanyawat 2014, Kaplan 1997, Moiz 2012, Molou 2014, Vulliamy 1988). Functional analyses of the variant protein shows decreased enzyme activity, increased affinity for G6P and decreased in vitro thermostability (Moiz 2012, Molou 2014, Vulliamy 1988). This variant is reported in ClinVar (Variation ID: 100057). This variant is found predominantly in the South Asian population with an allele frequency of 1.7% (331/19,078 alleles, including 4 homozygotes and 211 hemizygotes) in the Genome Aggregation Database. The serine at codon 188 is moderately conserved, but computational analyses predict that this variant is deleterious (REVEL: 0.811). Based on available information, this variant is considered to be pathogenic. References: Hellani A et al. G6PD Mediterranean S188F codon mutation is common among Saudi sickle cell patients and increases the risk of stroke. Genet Test Mol Biomarkers. 2009 Aug;13(4):449-52. Jamornthanyawat N et al. A population survey of the glucose-6-phosphate dehydrogenase (G6PD) 563C>T (Mediterranean) mutation in Afghanistan. PLoS One. 2014 Feb 21;9(2):e88605. Kaplan M et al. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12128-32. Moiz B et al. Neonatal hyperbilirubinemia in infants with G6PD c.563C > T Variant. BMC Pediatr. 2012 Aug 20;12:126. Molou E et al. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in Greek newborns: the Mediterranean C563T mutation screening. Scand J Clin Lab Invest. 2014 Apr;74(3):259-63. Vulliamy TJ et al. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5171-5.

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV001150542.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	144	not provided	not provided	clinical testing	not provided

Description

G6PD: PP1:Strong, PS4, PS3:Moderate

#	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		144	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447745.1

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

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001741952.3

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

#	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 Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807662.1

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

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001928877.1

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

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001976349.1

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

#	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 Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital, SCV002818285.1

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

#	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 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004024683.3

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

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004225543.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	9	not provided	not provided	clinical testing	PubMed (5)

#	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		9	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005197994.1

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

#	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: Oct 13, 2024

Relating variation to medicine