NM_000402.4(G6PD):c.934G>C (p.Asp312His) AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jun 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:: RCV000757322.43

Allele description [Variation Report for NM_000402.4(G6PD):c.934G>C (p.Asp312His)]

NM_000402.4(G6PD):c.934G>C (p.Asp312His)

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.934G>C (p.Asp312His)

Other names:

G6PD, ASP282HIS; G6PD Athens-like; G6PD Ferrara-II; G6PD Lodi; G6PD Modena; G6PD Seattle

HGVS:

NC_000023.11:g.154533596C>G
NG_009015.2:g.18977G>C
NM_000402.4:c.934G>C
NM_001042351.3:c.844G>C
NM_001360016.2:c.844G>CMANE SELECT
NP_000393.4:p.Asp312His
NP_001035810.1:p.Asp282His
NP_001035810.1:p.Asp282His
NP_001346945.1:p.Asp282His
NC_000023.10:g.153761811C>G
NM_000402.3:c.934G>C
NM_001042351.1:c.844G>C
NM_001042351.2:c.844G>C
NM_001042351.3:c.844G>C
NM_001360016.2:c.844G>C

Protein change:

D282H; ASP282HIS

Links:

OMIM: 305900.0010; dbSNP: rs137852318

NCBI 1000 Genomes Browser:

rs137852318

Molecular consequence:

NM_000402.4:c.934G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042351.3:c.844G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001360016.2:c.844G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000232594	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Nov 12, 2013)	germline	clinical testing	Citation Link,
SCV000885497	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Aug 1, 2017)	germline	clinical testing	Citation Link,
SCV001446885	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]
SCV001715686	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 21, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 2912069, 7947250, 10782016, 25741868
SCV001747681	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jun 1, 2024)	germline	clinical testing	Citation Link,
SCV001983798	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 23, 2022)	germline	clinical testing	Citation Link,
SCV005197993	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 19, 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	16	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	8	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two point mutations are responsible for G6PD polymorphism in Sardinia.

De Vita G, Alcalay M, Sampietro M, Cappelini MD, Fiorelli G, Toniolo D.

Am J Hum Genet. 1989 Feb;44(2):233-40.

PubMed [citation]

PMID:: 2912069
PMCID:: PMC1715414

Biochemical and molecular characterization of a new sporadic glucose-6-phosphate dehydrogenase variant described in Italy: G6PD Modena.

Cappellini MD, Sampietro M, Toniolo D, Carandina G, Pittalis S, Martinez di Montemuros F, Tavazzi D, Fiorelli G.

Br J Haematol. 1994 May;87(1):209-11.

PubMed [citation]

PMID:: 7947250

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000232594.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	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		6	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885497.1

#	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.844G>C; p.Asp282His variant (rs137852318), also known as G6PD Seattle/Ferrara II/Modena/Athens-like, has been reported in multiple individuals in the Mediterranean region with G6PD deficiency (Cappellini 1994, Cappellini 1995, De Vita 1989, Frigerio 1994, Lenzerini 1969, Rattazzi 1969). Functional characterization indicates enzymatic activity ranging from 15 to 25 percent of wildtype (Cappellini 1994, Cappellini 1995, De Vita 1989, Frigerio 1994, Lenzerini 1969, Rattazzi 1969), consistent with a class III variant (WHO working group 1989). The variant is listed as pathogenic in ClinVar (Variation ID: 10372), and observed in the general population databases at a frequency of 0.07% (143/200329 alleles, including 52 hemizygotes) in the Genome Aggregation Database. The aspartate at codon 282 is moderately conserved, and computational algorithms (Mutation Taster, PolyPhen-2, SIFT) predict that the variant has an impact on the protein. Based on the available information, this variant is classified as pathogenic. REFERENCES Cappellini M et al. Biochemical and molecular characterization of a new sporadic glucose-6-phosphate dehydrogenase variant described in Italy: G6PD Modena. Br J Haematol. 1994; 87(1):209-11. Cappellini M et al. Molecular characterisation of the glucose-6-phosphate dehydrogenase (G6PD) Ferrara II variant. Hum Genet. 1995; 95(4):440-2. De Vita G et al. Two point mutations are responsible for G6PD polymorphism in Sardinia. Am J Hum Genet. 1989; 44(2):233-40. Frigerio R et al. Molecular and biochemical data on some glucose-6-phosphate dehydrogenase variants from southern Sardinia. Haematologica. 1994; 79(4):319-21. Lenzerin L et al. Characterization of glucose-6-phosphate dehydrogenase variants. I. Occurrence of a G6PD Seattle-like variant in Sardinia and its interaction with the G6PD Mediterranean variant. Am J Hum Genet. 1969; 21(2):142-53. Rattazzi M et al. Characterization of glucose-6-phosphate dehydrogenase variants. II. G6PD Kephalonia, G6PD Attica, and G6PD Seattle-like" found in Greece. Am J Hum Genet. 1969; 21(2):154-67. WHO working group. Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ. 1989; 67(6):601-11. "

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446885.1

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV001715686.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

#	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		2	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001747681.20

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	16	not provided	not provided	clinical testing	not provided

Description

G6PD: PP1:Strong, PM5, PS3:Moderate, PS4:Moderate, PM2:Supporting

#	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		16	not provided	not provided	not provided

From GeneDx, SCV001983798.2

#	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 that this variant reduces enzyme activity to 20% of wild type enzyme, and is associated with a mild form of G6PD deficiency (De Vita et al., 1989); This variant is associated with the following publications: (PMID: 2912069, 26990548, 30096395, 31681265, 7806085, 7947250, 8807321, 5305539, 7947239, 5770172, 4974311, 9299858, 34426522, 28902532, 35725860)

#	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 Laboratory, Skane University Hospital Lund, SCV005197993.1

#	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: Nov 10, 2024

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