chr16-4505561-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002134.4(HMOX2):c.37G>A(p.Glu13Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,606,662 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 (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
HMOX2
NM_002134.4 missense
NM_002134.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 5.35
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08405632).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HMOX2 | NM_002134.4 | c.37G>A | p.Glu13Lys | missense_variant | 2/6 | ENST00000570646.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HMOX2 | ENST00000570646.6 | c.37G>A | p.Glu13Lys | missense_variant | 2/6 | 1 | NM_002134.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152162
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000461 AC: 11AN: 238472Hom.: 0 AF XY: 0.0000465 AC XY: 6AN XY: 128974
GnomAD3 exomes
AF:
AC:
11
AN:
238472
Hom.:
AF XY:
AC XY:
6
AN XY:
128974
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000131 AC: 19AN: 1454382Hom.: 0 Cov.: 30 AF XY: 0.00000968 AC XY: 7AN XY: 722808
GnomAD4 exome
AF:
AC:
19
AN:
1454382
Hom.:
Cov.:
30
AF XY:
AC XY:
7
AN XY:
722808
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74450
GnomAD4 genome
AF:
AC:
5
AN:
152280
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74450
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
4
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 | Jun 28, 2022 | The c.37G>A (p.E13K) alteration is located in exon 3 (coding exon 1) of the HMOX2 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the glutamic acid (E) at amino acid position 13 to be replaced by a lysine (K). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;T;T;T;T;.;T;T;.;T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;.;.;D;.;D;D;D;D;D;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;L;L;L;L;.;.;.;.;.;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.;N;.;.;N;.;.;.;.;.;N;N;.
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
Polyphen
0.87
.;P;P;P;P;P;P;.;.;.;.;.;P;P;.
Vest4
0.57, 0.57, 0.57, 0.57, 0.54
MVP
MPC
0.14
ClinPred
T
GERP RS
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