chr16-4505561-G-A

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

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.35
Variant links:
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
HMOX2NM_002134.4 linkuse as main transcriptc.37G>A p.Glu13Lys missense_variant 2/6 ENST00000570646.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMOX2ENST00000570646.6 linkuse as main transcriptc.37G>A p.Glu13Lys missense_variant 2/61 NM_002134.4 P1P30519-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000461
AC:
11
AN:
238472
Hom.:
0
AF XY:
0.0000465
AC XY:
6
AN XY:
128974
show subpopulations
Gnomad AFR exome
AF:
0.0000676
Gnomad AMR exome
AF:
0.000239
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000188
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000131
AC:
19
AN:
1454382
Hom.:
0
Cov.:
30
AF XY:
0.00000968
AC XY:
7
AN XY:
722808
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000160
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000235
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000722
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000330
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 submitterclinical testingAmbry GeneticsJun 28, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;T;T;T;T;T;T;T;.;T;T;.;T;T;T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D;.;.;.;.;D;.;D;D;D;D;D;.;.;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.084
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;L;L;L;L;L;L;.;.;.;.;.;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.74
.;N;.;N;.;.;N;.;.;.;.;.;N;N;.
REVEL
Benign
0.12
Sift
Uncertain
0.013
.;D;.;D;.;.;D;.;.;.;.;.;D;D;.
Sift4G
Benign
0.23
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
0.58
MPC
0.14
ClinPred
0.093
T
GERP RS
5.7
Varity_R
0.16
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139017711; hg19: chr16-4555562; COSMIC: COSV54861724; COSMIC: COSV54861724; API