chr16-4507002-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002134.4(HMOX2):āc.194A>Gā(p.Glu65Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000382 in 1,605,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.00040 ( 0 hom. )
Consequence
HMOX2
NM_002134.4 missense
NM_002134.4 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 6.72
Genes affected
HMOX2 (HGNC:5014): (heme oxygenase 2) Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3295226).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HMOX2 | NM_002134.4 | c.194A>G | p.Glu65Gly | missense_variant | 3/6 | ENST00000570646.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HMOX2 | ENST00000570646.6 | c.194A>G | p.Glu65Gly | missense_variant | 3/6 | 1 | NM_002134.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152060Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000219 AC: 55AN: 251480Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135918
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GnomAD4 exome AF: 0.000405 AC: 588AN: 1453086Hom.: 0 Cov.: 27 AF XY: 0.000384 AC XY: 278AN XY: 723490
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74266
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2021 | The c.194A>G (p.E65G) alteration is located in exon 4 (coding exon 2) of the HMOX2 gene. This alteration results from a A to G substitution at nucleotide position 194, causing the glutamic acid (E) at amino acid position 65 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;T;T;T;.;T;.;T;T;.;T;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;.;.;D;.;D;D;D;D;D;D;.;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;M;M;M;M;.;.;.;.;.;.;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
REVEL
Benign
Sift
Uncertain
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.98
.;D;D;D;D;D;D;.;.;.;.;.;.;D;D;.
Vest4
0.52, 0.53, 0.51, 0.52
MVP
MPC
0.23
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at