rs281860626
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM4_SupportingPP5_Moderate
The NM_000517.6(HBA2):c.114_115insGAA(p.Pro38_Thr39insGlu) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 10)
Consequence
HBA2
NM_000517.6 inframe_insertion
NM_000517.6 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.517
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 5 ACMG points.
PM1
?
In a hotspot region, there are 7 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_000517.6
PM4
?
Nonframeshift variant in NON repetitive region in NM_000517.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 16-173143-C-CGAA is Pathogenic according to our data. Variant chr16-173143-C-CGAA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 619846.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA2 | NM_000517.6 | c.114_115insGAA | p.Pro38_Thr39insGlu | inframe_insertion | 2/3 | ENST00000251595.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.114_115insGAA | p.Pro38_Thr39insGlu | inframe_insertion | 2/3 | 1 | NM_000517.6 | P1 | |
HBA2 | ENST00000484216.1 | c.83_84insGAA | p.Pro28_Thr29insGlu | inframe_insertion | 2/2 | 1 | |||
HBA2 | ENST00000482565.1 | n.250_251insGAA | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
HBA2 | ENST00000397806.1 | c.18_19insGAA | p.Pro6_Thr7insGlu | inframe_insertion | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 10
GnomAD3 genomes
?
Cov.:
10
GnomAD4 exome Cov.: 9
GnomAD4 exome
Cov.:
9
GnomAD4 genome ? Cov.: 10
GnomAD4 genome
?
Cov.:
10
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 30, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at