rs281864813
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6_Moderate
The NM_000517.6(HBA2):c.59C>A(p.Ala20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Consequence
NM_000517.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.59C>A | p.Ala20Glu | missense_variant | Exon 1 of 3 | 1 | NM_000517.6 | ENSP00000251595.6 | ||
HBA2 | ENST00000484216.1 | c.26C>A | p.Ala9Glu | missense_variant | Exon 1 of 2 | 1 | ENSP00000495899.1 | |||
HBA2 | ENST00000482565.1 | n.78C>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 | |||||
HBA2 | ENST00000397806.1 | c.-2+13C>A | intron_variant | Intron 1 of 2 | 2 | ENSP00000380908.1 |
Frequencies
GnomAD3 genomes Cov.: 2
GnomAD4 exome Cov.: 0
GnomAD4 genome Cov.: 2
ClinVar
Submissions by phenotype
not provided Benign:1
The Hb J-Tashikuergan variant (HBA2: c.59C>A; p.Ala20Glu, also known as Asp19Glu when numbered from the mature protein, rs281864813, HbVar ID: 25) is reported in the literature in individuals with normal hematology (Xu 2021, HbVar database and references therein). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.52), but functional studies suggest it has normal stability, although it may interfere with measurement of HbA1c (Xu 2021, HbVar database and references therein). Based on available information, this variant is considered to be likely benign. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Xu J et al. Unexpected HbA1c results in the presence of three rare hemoglobin variants. Scand J Clin Lab Invest. 2021 Feb;81(1):59-64. PMID: 33315479. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at