rs281864838
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000517.6(HBA2):c.161C>A(p.Ala54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Genomes: not found (cov: 14)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HBA2
NM_000517.6 missense
NM_000517.6 missense
Scores
4
4
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.108
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 2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HBA2 | ENST00000251595.11 | c.161C>A | p.Ala54Asp | missense_variant | Exon 2 of 3 | 1 | NM_000517.6 | ENSP00000251595.6 | ||
| HBA2 | ENST00000484216.1 | c.128C>A | p.Ala43Asp | missense_variant | Exon 2 of 2 | 1 | ENSP00000495899.1 | |||
| HBA2 | ENST00000482565.1 | n.297C>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 1 | |||||
| HBA2 | ENST00000397806.1 | c.65C>A | p.Ala22Asp | missense_variant | Exon 2 of 3 | 2 | ENSP00000380908.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
14
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000111 AC: 1AN: 901914Hom.: 0 Cov.: 12 AF XY: 0.00000216 AC XY: 1AN XY: 463314
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
901914
Hom.:
Cov.:
12
AF XY:
AC XY:
1
AN XY:
463314
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
14
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Benign
T;T
Vest4
MutPred
Loss of methylation at K57 (P = 0.069);.;
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at