rs281860615
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PP3_StrongBP6
The NM_000517.6(HBA2):c.273G>T(p.Lys91Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000859 in 1,396,262 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K91R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000517.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA2 | NM_000517.6 | c.273G>T | p.Lys91Asn | missense_variant | 2/3 | ENST00000251595.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.273G>T | p.Lys91Asn | missense_variant | 2/3 | 1 | NM_000517.6 | P1 | |
HBA2 | ENST00000484216.1 | c.243G>T | p.Lys81Asn | missense_variant | 2/2 | 1 | |||
HBA2 | ENST00000482565.1 | n.409G>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
HBA2 | ENST00000397806.1 | c.177G>T | p.Lys59Asn | missense_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome AF: 0.00000859 AC: 12AN: 1396262Hom.: 0 Cov.: 27 AF XY: 0.0000101 AC XY: 7AN XY: 693700
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Feb 13, 2023 | The HBA2 c.273G>T (p.Lys91Asn) variant is described to have normal oxygen affinity and relative stability, with quantities in heterozygotes at 24-25%. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In heterozygotes, the variant is clinically silent with hematological parameters within normal limits and normal peripheral blood morphology (PMIDs: 7803274 (1994), 740406 (1978), 5452727 (1970)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. 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 | Sep 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at