Submissions for variant G6PD NARA

dbSNP: rs587776730

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001509137	SCV001473440	likely pathogenic	not provided	2019-09-19	criteria provided, single submitter	clinical testing	The G6PD c.957_980del; p.Lys320_Thr327del variant (rs587776730), also known as G6PD Nara, is reported in the literature in an individual affected with G6PD deficiency (Hirono 1993). This variant deletes eight amino acids, leaving the rest of the protein in-frame. Functional analysis of hemolysate from an affected individual with this variant showed no detectable G6PD activity, and the variant protein was reported to be extremely thermolabile with rapid loss of residual enzyme activity (Hirono 1993). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Based on available information, this variant is considered to be likely pathogenic. References: Hirono A et al. G6PD Nara: a new class 1 glucose-6-phosphate dehydrogenase variant with an eight amino acid deletion. Blood. 1993 Dec 1;82(11):3250-2.
Mayo Clinic Laboratories, Mayo Clinic	RCV001509137	SCV001715684	likely pathogenic	not provided	2020-12-29	criteria provided, single submitter	clinical testing	PM2, PM4, PP4, PS4_supporting
Johns Hopkins Genomics, Johns Hopkins University	RCV000143789	SCV002570289	likely pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2022-02-21	criteria provided, single submitter	clinical testing	This G6PD variant (rs587776730) is absent from a large population dataset and has been reported to ClinVar. This Class I variant, sometimes referred to as "G6PD Nara", has been identified in three unrelated males with chronic-hemolytic anemia. This 24-bp deletion in exon 9 of the G6PD gene removes eight amino acids, leaving the rest of the protein in-frame. No measurable G6PD activity was detected in the hemolysate of a patient with this variant, and the partially purified protein was reported to be extremely thermolabile with rapid loss of activity. This variant was also identified in the patient's asymptomatic mother (JHG1850-2). Based on the available evidence, we consider this variant to be likely pathogenic.
Dunham Lab, University of Washington	RCV000143789	SCV002599351	pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2022-08-12	criteria provided, single submitter	curation	Variant found in unrelated hemizygotes with deficiency and CNSHA (PS4_M, PP4). No detectable activity in red blood cells (PS3). Leads to deletion of eight amino acids (PM4). Not found in gnomAD (PM2). Post_P 0.997 (odds of pathogenicity 3158, Prior_P 0.1).
Invitae	RCV000143789	SCV003496308	uncertain significance	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2023-05-01	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with G6PD deficiency (PMID: 8241497, 16753852; Invitae). 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. This variant disrupts a region of the G6PD protein in which other variant(s) (p.Tyr322His) have been observed in individuals with G6PD-related conditions (PMID: 11112389). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 10411). This variant is not present in population databases (gnomAD no frequency). This variant, c.957_980del, results in the deletion of 8 amino acid(s) of the G6PD protein (p.Lys320_Thr327del), but otherwise preserves the integrity of the reading frame.
Revvity Omics, Revvity	RCV000143789	SCV003833832	likely pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	2022-05-31	criteria provided, single submitter	clinical testing
OMIM	RCV000143789	SCV000188683	pathogenic	Anemia, nonspherocytic hemolytic, due to G6PD deficiency	1993-12-01	no assertion criteria provided	literature only