rs1165799259
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000517.6(HBA2):c.*82G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,569,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 25)
Exomes 𝑓: 0.0000092 ( 1 hom. )
Consequence
HBA2
NM_000517.6 3_prime_UTR
NM_000517.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.521
Genes affected
HBA2 (HGNC:4824): (hemoglobin subunit alpha 2) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA2 | NM_000517.6 | c.*82G>A | 3_prime_UTR_variant | 3/3 | ENST00000251595.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.*82G>A | 3_prime_UTR_variant | 3/3 | 1 | NM_000517.6 | P1 | ||
HBA2 | ENST00000397806.1 | c.*82G>A | 3_prime_UTR_variant | 3/3 | 2 | ||||
ENST00000702607.1 | upstream_gene_variant | ||||||||
HBA2 | ENST00000482565.1 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000670 AC: 1AN: 149234Hom.: 0 Cov.: 25
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GnomAD4 exome AF: 0.00000915 AC: 13AN: 1420724Hom.: 1 Cov.: 26 AF XY: 0.0000113 AC XY: 8AN XY: 707140
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GnomAD4 genome ? AF: 0.00000670 AC: 1AN: 149234Hom.: 0 Cov.: 25 AF XY: 0.0000137 AC XY: 1AN XY: 72792
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 25, 2016 | - - |
Computational scores
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Name
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Benign
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Benign
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Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at