ClinVar Miner

Submissions for variant NM_000402.4(G6PD):c.1478G>A (p.Arg493His) (rs72554664)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174271 SCV000225547 pathogenic not provided 2013-05-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508383 SCV000603772 pathogenic none provided 2019-09-25 criteria provided, single submitter clinical testing The G6PD c.1388G>A; p.Arg463His variant (rs72554664), also known as G6PD Kaiping, is reported in the literature as a common G6PD deficiency variant in Asian populations (Chiu 1991, Fu 2018, Li 1998, Nuchprayoon 2002). This variant is reported in ClinVar (Variation ID: 100059), and is found in the East Asian population with an allele frequency of 0.70% (104/14782 alleles, including 32 hemizygotes and a single homozygote) in the Genome Aggregation Database. The arginine at codon 463 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other variants at this codon (c.1387C>T; p.Arg463Cys, c.1387C>A; p.Arg462Ser) have been reported in individuals with G6PD deficiency (Hirono 1997, Rodrigues 2002). Based on available information, the p.Arg463His variant is considered to be pathogenic. References: Chiu DT et al. Two commonly occurring nucleotide base substitutions in Chinese G6PD variants. Biochem Biophys Res Commun. 1991 180(2):988-93. Fu C et al. Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates. Sci Rep. 2018 Jan 16;8(1):833. Hirono A et al. Molecular analysis of eight biochemically unique glucose-6-phosphate dehydrogenase variants found in Japan. Blood. 1997 Jun 15;89(12):4624-7. Li P et al. Analysis of common mutations and associated haplotypes in Chinese patients with glucose-6-phosphate dehydrogenase deficiency. Biochem Mol Biol Int. 1998 46(6):1135-43. Nuchprayoon I et al. Glucose-6-phosphate dehydrogenase (G6PD) mutations in Thailand: G6PD Viangchan (871G>A) is the most common deficiency variant in the Thai population. Hum Mutat. 2002 Feb;19(2):185. Rodrigues MO et al. Glucose-6-phosphate dehydrogenase deficiency in Portugal: biochemical and mutational profiles, heterogeneity, and haplotype association. Blood Cells Mol Dis. 2002 Mar-Apr;28(2):249-59.
Fulgent Genetics,Fulgent Genetics RCV000763201 SCV000893820 pathogenic Susceptibility to malaria; Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000823393 SCV000964252 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 463 of the G6PD protein (p.Arg463His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs72554664, ExAC 0.5%). This variant has been described as a common cause of glucose-6-phosphate dehydrogenase deficiency in Southeast Asia, although it has also been reported in affected individuals from other populations (PMID: 9589612, 30315739, 17726510, 21446359, 15906717, 15223006, 20236109). ClinVar contains an entry for this variant (Variation ID: 100059). This variant is also known as Kaiping in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266661 SCV001444838 pathogenic Inborn genetic diseases 2016-06-10 criteria provided, single submitter clinical testing
OMIM RCV000011120 SCV000031347 other G6PD KAIPING 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011121 SCV000031348 other G6PD ANANT 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011122 SCV000031349 other G6PD DHON 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011123 SCV000031350 other G6PD PETRICH-LIKE 2017-05-24 no assertion criteria provided literature only
OMIM RCV000011124 SCV000031351 other G6PD SAPPORO-LIKE 2017-05-24 no assertion criteria provided literature only
Reproductive Health Research and Development,BGI Genomics RCV000991190 SCV001142503 pathogenic Glucose 6 phosphate dehydrogenase deficiency 2020-01-06 no assertion criteria provided curation NM_001042351.1:c.1388G>A in the G6PD gene has an allele frequency of 0.007 in East Asian subpopulation in the gnomAD database. This variant has been described as a common cause of glucose-6-phosphate dehydrogenase deficiency in Southeast Asia, although it has also been reported in affected individuals from other populations (PMID: 9589612, 30315739, 17726510, 21446359, 15906717, 15223006, 20236109). Experimental studies have shown that this missense change causes a significant reduction in enzyme activity and affinity for glucose-6-phosphate (PMID: 16607506). Pathogenic computational verdict because pathogenic predictions from DANN, DEOGEN2, FATHMM-MKL, M-CAP, MVP, MutationAssessor, MutationTaster, REVEL and SIFTT. aken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PS3; PS4; PP4.

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