Submissions for variant NM_000517.6(HBA2):c.369C>G (p.His123Gln)

dbSNP: rs41479347

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000985723	SCV000603878	uncertain significance	not provided	2023-04-27	criteria provided, single submitter	clinical testing	The Hb Westmead variant (HBA2: c.369C>G; p.His123Gln, also known as His122Gln when numbered from the mature protein, rs41479347, HbVar ID: 185) has been reported in the heterozygous state in multiple individuals of East Asian descent, but has not been associated with significant clinical symptoms (Jiang 2020, Ma 2001, Viprakasit 2014, Wong 2004, HbVar database and references therein). This variant has been reported in homozygous individuals with mild anemia (Jiang 2020). However, it is an unstable hemoglobin variant, and its co-occurrence with beta thalassemia results in milder symptoms for the patient (Scheps 2020, Wong 2004, HbVar database and references therein). This variant is reported in ClinVar (Variation ID: 439771). It is found in the East Asian population with an overall allele frequency of 0.17% (33/19844 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.618). However, given the lack of clinical and functional data, the significance of the p.His123Gln variant is uncertain at this time. References: HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Jiang F et al. Hb Westmead (HBA2: c.369C>G): Hematological Characteristics in Heterozygotes with and without a0-Thalassemia. Hemoglobin. 2020 May;44(3):153-155. PMID: 32436451. Ma E et al. Interaction between (--SEA) alpha-thalassemia deletion and uncommon non-deletional alpha-globin gene mutations in Chinese patients. Haematologica. 2001; 86(5):539-40. PMID: 11410420. Scheps KG et al. Curating the gnomAD database: Report of novel variants in the globin-coding genes and bioinformatics analysis. Hum Mutat. 2020 Jan;41(1):81-102. PMID: 31553106. Viprakasit V et al. Clinical presentation and molecular identification of four uncommon alpha globin variants in Thailand. Acta Haematol. 2014;131(2):88-94. PMID: 24081251. Wong W et al. Thalassemia intermedia due to co-inheritance of beta0/beta(+)-thalassemia and (--SEA) alpha-thalassemia/Hb Westmead (alpha122(H5)His > Gln (alpha2)) in a Chinese family. Hemoglobin. 2004; 28(2):151-6. PMID: 15182058.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985723	SCV001134196	uncertain significance	not provided	2020-04-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002476016	SCV002803820	uncertain significance	Heinz body anemia; alpha Thalassemia; Hemoglobin H disease; Erythrocytosis, familial, 7	2022-04-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001275681	SCV003835913	uncertain significance	alpha Thalassemia	2022-11-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147493	SCV003835914	uncertain significance	Erythrocytosis, familial, 7	2022-11-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147491	SCV003836044	uncertain significance	Hemoglobin H disease	2022-11-29	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003147492	SCV003836057	uncertain significance	Heinz body anemia	2022-11-29	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001275681	SCV005416062	likely pathogenic	alpha Thalassemia		criteria provided, single submitter	clinical testing	PM3_VeryStrong+PP4
OMIM	RCV002282188	SCV000037450	other	HEMOGLOBIN WESTMEAD	2018-05-10	no assertion criteria provided	literature only
Natera, Inc.	RCV001275681	SCV001461040	uncertain significance	alpha Thalassemia	2020-09-16	no assertion criteria provided	clinical testing