NM_000402.4(G6PD):c.1406G>C (p.Arg469Pro) AND Anemia, nonspherocytic hemolytic, due to G6PD deficiency

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Sep 30, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000011139.18

Allele description [Variation Report for NM_000402.4(G6PD):c.1406G>C (p.Arg469Pro)]

NM_000402.4(G6PD):c.1406G>C (p.Arg469Pro)

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.1406G>C (p.Arg469Pro)

Other names:

G6PD, ARG439PRO; G6PD Pawnee

HGVS:

NC_000023.11:g.154532434C>G
NG_009015.2:g.20139G>C
NM_000402.4:c.1406G>C
NM_001042351.3:c.1316G>C
NM_001360016.2:c.1316G>CMANE SELECT
NP_000393.4:p.Arg469Pro
NP_001035810.1:p.Arg439Pro
NP_001346945.1:p.Arg439Pro
NC_000023.10:g.153760649C>G
NM_001042351.1:c.1316G>C
NM_001042351.3:c.1316G>C

Protein change:

R439P; ARG439PRO

Links:

OMIM: 305900.0040; dbSNP: rs137852337

NCBI 1000 Genomes Browser:

rs137852337

Molecular consequence:

NM_000402.4:c.1406G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042351.3:c.1316G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001360016.2:c.1316G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Anemia, nonspherocytic hemolytic, due to G6PD deficiency (CNSHA1)
Synonyms:: Hemolytic anemia due to G6PD deficiency; Favism, susceptibility to; Class I glucose-6-phosphate dehydrogenase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010480; MedGen: C2720289; Orphanet: 466026; OMIM: 300908

Recent activity

Clear Turn Off Turn On

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
SCV002599281	Dunham Lab, University of Washington	criteria provided, single submitter (Bayesian ACMG Guidelines, 2018)	Likely pathogenic (Aug 12, 2022)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 1611091, 29300386
SCV003251382	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 30, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 1611091, 28492532
SCV003833843	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005374540	OMIM	no assertion criteria provided	Pathogenic (Oct 11, 2024)	germline	literature only	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	unknown	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework.

Tavtigian SV, Greenblatt MS, Harrison SM, Nussbaum RL, Prabhu SA, Boucher KM, Biesecker LG; ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI)..

Genet Med. 2018 Sep;20(9):1054-1060. doi: 10.1038/gim.2017.210. Epub 2018 Jan 4.

PubMed [citation]

PMID:: 29300386
PMCID:: PMC6336098

New glucose-6-phosphate dehydrogenase mutations from various ethnic groups.

Beutler E, Westwood B, Prchal JT, Vaca G, Bartsocas CS, Baronciani L.

Blood. 1992 Jul 1;80(1):255-6.

PubMed [citation]

PMID:: 1611091

See all PubMed Citations (5)

Details of each submission

From Dunham Lab, University of Washington, SCV002599281.1

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

Description

Variant found in hemizygote with G6PD deficiency and CNSHA (PP4). Decreased activity in red blood cells (7%) (PS3). Not found in gnomAD (PM2). Reported as pathogenic by clinical testing group (PP5). Post_P 0.975 (odds of pathogenicity 350.3, Prior_P 0.1).

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003251382.1

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

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 439 of the G6PD protein (p.Arg439Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of G6PD defiency (PMID: 1611091). This variant is also known as the Pawnee variant. ClinVar contains an entry for this variant (Variation ID: 10399). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt G6PD protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Revvity Omics, Revvity, SCV003833843.2

#	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 OMIM, SCV005374540.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a US white patient with nonspherocytic hemolytic anemia (CNSHA1; 300908), Beutler et al. (1992) identified a G-to-C transition at nucleotide 1316 leading to an arg439-to-pro substitution.

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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine