Genetic Variant HMOX2:p.Ser34Ser (chr16-4506910-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002134.4(HMOX2):c.102G>A(p.Ser34Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,612,734 control chromosomes in the GnomAD database, including 2,607 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.081 ( 800 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1807 hom. )

Consequence

HMOX2
NM_002134.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.26

Publications

8 publications found

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]

HMOX2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=-4.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX2	NM_002134.4 link	c.102G>A	p.Ser34Ser	synonymous_variant	Exon 3 of 6	ENST00000570646.6	NP_002125.3	P30519-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6 link	c.102G>A	p.Ser34Ser	synonymous_variant	Exon 3 of 6	1	NM_002134.4	ENSP00000459214.1		P30519-1

Frequencies

GnomAD3 genomes

AF:

0.0809

AC:

12293

AN:

151972

Hom.:

798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0498

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.0280

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0379

Gnomad OTH

AF:

0.0720

GnomAD2 exomes

AF:

0.0516

AC:

12978

AN:

251440

AF XY:

0.0449

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0369

Gnomad OTH exome

AF:

0.0450

GnomAD4 exome

AF:

0.0409

AC:

59801

AN:

1460642

Hom.:

1807

Cov.:

AF XY:

0.0395

AC XY:

28702

AN XY:

726770

show subpopulations

African (AFR)

AF:

0.177

AC:

5914

AN:

33408

American (AMR)

AF:

0.118

AC:

5259

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

1377

AN:

26124

East Asian (EAS)

AF:

0.00403

AC:

160

AN:

39696

South Asian (SAS)

AF:

0.0163

AC:

1409

AN:

86256

European-Finnish (FIN)

AF:

0.0260

AC:

1388

AN:

53418

Middle Eastern (MID)

AF:

0.0279

AC:

161

AN:

5762

European-Non Finnish (NFE)

AF:

0.0373

AC:

41388

AN:

1110900

Other (OTH)

AF:

0.0455

AC:

2745

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

2500

5000

7501

10001

12501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1642

3284

4926

6568

8210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0809

AC:

12300

AN:

152092

Hom.:

800

Cov.:

AF XY:

0.0792

AC XY:

5888

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.175

AC:

7238

AN:

41458

American (AMR)

AF:

0.116

AC:

1776

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

173

AN:

3472

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.0152

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0280

AC:

297

AN:

10594

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0378

AC:

2573

AN:

67982

Other (OTH)

AF:

0.0713

AC:

150

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

567

1133

1700

2266

2833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0588

Hom.:

191

Bravo

AF:

0.0921

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0401

EpiControl

AF:

0.0375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.8

(source)

DANN

Benign

0.82

PhyloP100

-4.3

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over