rs281864817
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP3BP6
The NM_000517.6(HBA2):āc.64G>Cā(p.Ala22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22D) has been classified as Likely benign.
Frequency
Consequence
NM_000517.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA2 | NM_000517.6 | c.64G>C | p.Ala22Pro | missense_variant | 1/3 | ENST00000251595.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.64G>C | p.Ala22Pro | missense_variant | 1/3 | 1 | NM_000517.6 | P1 | |
HBA2 | ENST00000484216.1 | c.34G>C | p.Ala12Pro | missense_variant | 1/2 | 1 | |||
HBA2 | ENST00000482565.1 | n.83G>C | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
HBA2 | ENST00000397806.1 | c.-2+18G>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 4754Hom.: 0 Cov.: 2 FAILED QC
GnomAD3 exomes AF: 0.0000188 AC: 1AN: 53330Hom.: 0 AF XY: 0.0000372 AC XY: 1AN XY: 26890
GnomAD4 exome AF: 0.0000219 AC: 9AN: 411840Hom.: 1 Cov.: 0 AF XY: 0.0000323 AC XY: 7AN XY: 216496
GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 4724Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0AN XY: 2328
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 13, 2023 | The Hb Fontainebleau variant is reported as having normal stability (PMID: 2599878 (2009)). The variant has also been reported in a screening study of alpha thalassemia carriers (PMID: 29627922 (2018)) and has been reported individuals with microcytosis (PMID: 22461654 (2012)) and without microcytosis (PMID: 19657841 (2009)). Based on the available information, we are unable to determine the clinical significance of this variant. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 23, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at