rs281860594
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000184.3(HBG2):c.217G>C(p.Gly73Arg) 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 other (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HBG2
NM_000184.3 missense
NM_000184.3 missense
Scores
5
3
4
Clinical Significance
Conservation
PhyloP100: 3.06
Genes affected
HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [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, 0.891
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBG2 | NM_000184.3 | c.217G>C | p.Gly73Arg | missense_variant | 2/3 | ENST00000336906.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBG2 | ENST00000336906.6 | c.217G>C | p.Gly73Arg | missense_variant | 2/3 | 1 | NM_000184.3 | P1 | |
HBG2 | ENST00000380252.6 | c.52G>C | p.Gly18Arg | missense_variant | 2/3 | 3 | |||
HBG2 | ENST00000444587.1 | c.*86G>C | 3_prime_UTR_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1461886Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1461886
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
727248
Gnomad4 AFR exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN F (MINOO) Other:1
other, no assertion criteria provided | literature only | OMIM | Aug 18, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
N;N;N
Polyphen
0.98
.;.;D;.
Vest4
0.53
MutPred
Gain of MoRF binding (P = 0.0096);Gain of MoRF binding (P = 0.0096);Gain of MoRF binding (P = 0.0096);.;
MVP
0.94
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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