16-172929-CCGA-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_000517.6(HBA2):c.19_21delGAC(p.Asp7del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Consequence
HBA2
NM_000517.6 conservative_inframe_deletion
NM_000517.6 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.93
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 Uncertain_significance. Variant got 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_000517.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HBA2 | ENST00000251595.11 | c.19_21delGAC | p.Asp7del | conservative_inframe_deletion | Exon 1 of 3 | 1 | NM_000517.6 | ENSP00000251595.6 | ||
| HBA2 | ENST00000482565.1 | n.38_40delGAC | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 | |||||
| HBA2 | ENST00000397806 | c.-29_-27delGAC | 5_prime_UTR_variant | Exon 1 of 3 | 2 | ENSP00000380908.1 | ||||
| HBA2 | ENST00000484216.1 | c.-16_-14delCGA | upstream_gene_variant | 1 | ENSP00000495899.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
0
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 08, 2024 | The Hb Boyle Heights variant (HBA2: c.19_21delGAC; p.Asp7del, also known as Asp6del when numbered from the mature protein, rs34623271, ClinVar ID: 15641, HbVar ID: 715) is reported in several heterozygous individuals with mild microcytosis and hypochromia without anemia (Johnson 1983, Zhao 1990, HbVar database). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant deletes a single aspartate residue leaving the rest of the protein in-frame. Functional characterization suggests the variant protein is unstable and exhibits increased oxygen affinity (Johnson 1983). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Johnson CS et al. The first example of a deletion in the human alpha chain: hemoglobin Boyle Heights or alpha 2 6 (A4) Asp----to O beta 2. Hemoglobin. 1983;7(2):125-40. PMID: 6671902. Zhao W et al. Low quantities of Hb Boyle Heights or alpha 2(6)(A4)Asp----O beta 2 observed in three members of a Caucasian family. Hemoglobin. 1990;14(6):637-40. PMID: 2101838 - |
HEMOGLOBIN BOYLE HEIGHTS Other:1
| other, no assertion criteria provided | literature only | OMIM | Sep 12, 2022 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at