ClinVar Miner

Submissions for variant NM_000517.6(HBA2):c.420del (p.Lys140fs) (rs63750520)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507225 SCV000601216 pathogenic not provided 2016-12-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002284 SCV001160167 uncertain significance none provided 2020-07-30 criteria provided, single submitter clinical testing The Hb Wayne variant (HBA2: c.420delA; p.Lys140fs, also known as Lys139fs when numbered from the mature protein; rs63750520) has been reported in individuals with no clinical abnormalities (Salkie 1992, Seid-Akhavan 1976, HbVar database); however, its phenotype in the presence of other pathogenic globin variants is uncertain. The variant hemoglobin comprises 4-6% (Seid-Akhavan 1976) or 12-16% of total hemoglobin (Huisman 1984), depending on the purification methodology. Functional characterization of the variant hemoglobin indicates increased oxygen affinity and strong reduction in Bohr effect (Huisman 1984). The variant is listed in ClinVar (Variation ID: 15629) and observed on a single chromosome in the Genome Aggregation Database general population database (1/249094 alleles). The variant causes a frameshift that replaces the last three amino acids with eight novel amino acids at the C terminus. Although the variant causes protein translation past the canonical termination codon, it is not predicted to impact the downstream polyadenylation site (PolyA signal miner). Due to the limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Link to HbVar database for Hb Wayne: Huisman T et al. Hb Wayne, the frameshift variant with extended alpha chains observed in a Caucasian family from Alabama. Hemoglobin. 1984; 8(1):1-15. Salkie M et al. A Canadian family with Hb Wayne; characterization by HPLC and DNA sequencing. Hemoglobin. 1992; 16(6):515-9. Seid-Akhavan M et al. Hemoglobin Wayne: a frameshift mutation detected in human hemoglobin alpha chains. Proc Natl Acad Sci U S A. 1976; 73(3):882-6.
OMIM RCV000016896 SCV000037167 other HEMOGLOBIN WAYNE 2013-03-28 no assertion criteria provided literature only

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