VCV001722746.6 - ClinVar

NM_001360016.2(G6PD):c.634A>G (p.Met212Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Likely pathogenic(2); Uncertain significance(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001360016.2(G6PD):c.634A>G (p.Met212Val)

Variation ID: 1722746 Accession: VCV001722746.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq28 X: 154534348 (GRCh38) [ NCBI UCSC ] X: 153762563 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Nov 13, 2022	Sep 16, 2024	Dec 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001360016.2:c.634A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001346945.1:p.Met212Val	missense
NM_000402.4:c.724A>G	NP_000393.4:p.Met242Val	missense
NM_001042351.3:c.634A>G	NP_001035810.1:p.Met212Val	missense
NC_000023.11:g.154534348T>C
NC_000023.10:g.153762563T>C
NG_009015.2:g.18225A>G

... more HGVS ... less HGVS

Protein change

M212V, M242V

Other names

G6PD Sibari

Canonical SPDI

NC_000023.11:154534347:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
G6PD		-	-	GRCh38 GRCh37	657	978

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Anemia, nonspherocytic hemolytic, due to G6PD deficiency	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Aug 12, 2022	RCV002305856.6
Malaria, susceptibility to	Likely pathogenic (1)	criteria provided, single submitter	Dec 22, 2022	RCV003464445.1
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 11, 2023	RCV004700722.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Aug 12, 2022)	criteria provided, single submitter (Bayesian ACMG Guidelines, 2018) Method: curation	Anemia, nonspherocytic hemolytic, due to G6PD deficiency Affected status: yes Allele origin: unknown	Dunham Lab, University of Washington Accession: SCV002599213.1 First in ClinVar: Nov 13, 2022 Last updated: Nov 13, 2022	Publications: PubMed (2) PubMed: 23006493‚ 8447319 Comment: Variant found in unrelated patients with deficiency (PS4_M, PP4). Decreased activity in red blood cells of hemizygotes (13-20%) (PS3). Below expected carrier frequency in gnomAD … (more) Variant found in unrelated patients with deficiency (PS4_M, PP4). Decreased activity in red blood cells of hemizygotes (13-20%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.988 (odds of pathogenicity 729.3, Prior_P 0.1). (less)
Likely pathogenic (Dec 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Malaria, susceptibility to Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004195411.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Uncertain significance (Mar 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Anemia, nonspherocytic hemolytic, due to G6PD deficiency Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003828417.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Uncertain significance (Dec 11, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005201603.1 First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024	Comment: Also known as G6PD Sibari; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with … (more) Also known as G6PD Sibari; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35313643, 8364584, 27391121, 34272389, 34551338, 26753754, 22293322, 8447319, 23006493) (less)

Comment:

Variant found in unrelated patients with deficiency (PS4_M, PP4). Decreased activity in red blood cells of hemizygotes (13-20%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.988 (odds of pathogenicity 729.3, Prior_P 0.1).

Comment:

Also known as G6PD Sibari; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35313643, 8364584, 27391121, 34272389, 34551338, 26753754, 22293322, 8447319, 23006493)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity.	Dallol A	Journal of translational medicine	2012	PMID: 23006493
Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency revealed by single-strand conformation and sequence analysis.	Calabrò V	American journal of human genetics	1993	PMID: 8447319

Text-mined citations for this variant ...

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_001360016.2(G6PD):c.634A>G (p.Met212Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...