chr16-4507002-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002134.4(HMOX2):ā€‹c.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

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72
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 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
HMOX2NM_002134.4 linkuse as main transcriptc.194A>G p.Glu65Gly missense_variant 3/6 ENST00000570646.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMOX2ENST00000570646.6 linkuse as main transcriptc.194A>G p.Glu65Gly missense_variant 3/61 NM_002134.4 P1P30519-1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152060
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000219
AC:
55
AN:
251480
Hom.:
0
AF XY:
0.000206
AC XY:
28
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.000466
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000405
AC:
588
AN:
1453086
Hom.:
0
Cov.:
27
AF XY:
0.000384
AC XY:
278
AN XY:
723490
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000526
Gnomad4 OTH exome
AF:
0.0000832
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152060
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000229
Hom.:
0
Bravo
AF:
0.000166
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000296
AC:
36
EpiCase
AF:
0.000164
EpiControl
AF:
0.000474

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 GeneticsDec 21, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
.;T;T;T;T;T;T;.;T;.;T;T;.;T;T;T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D;.;.;.;.;D;.;D;D;D;D;D;D;.;.;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
.;M;M;M;M;M;M;.;.;.;.;.;.;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-4.8
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
REVEL
Benign
0.27
Sift
Uncertain
0.019
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
Sift4G
Benign
0.17
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
0.59
MPC
0.23
ClinPred
0.56
D
GERP RS
5.8
Varity_R
0.79
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs140785119; hg19: chr16-4557003; API