NM_002134.4:c.555G>A

Variant names:

• chr16-4508063-G-A
• rs2404579
• NM_002134.4:c.555G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002134.4(HMOX2):​c.555G>A​(p.Gln185Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,614,158 control chromosomes in the GnomAD database, including 18 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 0.0031 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (15 hom.)
• Consequence: HMOX2 NM_002134.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.02 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002134.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	NM_002134.4	MANE Select	c.555G>A	p.Gln185Gln	synonymous	Exon 4 of 6	NP_002125.3
	HMOX2	NM_001286267.2		c.717G>A	p.Gln239Gln	synonymous	Exon 5 of 7	NP_001273196.1
	HMOX2	NM_001127204.2		c.555G>A	p.Gln185Gln	synonymous	Exon 5 of 7	NP_001120676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	ENST00000570646.6	TSL:1 MANE Select	c.555G>A	p.Gln185Gln	synonymous	Exon 4 of 6	ENSP00000459214.1
	HMOX2	ENST00000613539.1	TSL:5	c.717G>A	p.Gln239Gln	synonymous	Exon 4 of 6	ENSP00000477572.1
	HMOX2	ENST00000219700.10	TSL:5	c.555G>A	p.Gln185Gln	synonymous	Exon 4 of 6	ENSP00000219700.6

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152168 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00538

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00265 AC: 666 AN: 251366 AF XY: 0.00266

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00451

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00433 AC: 6333 AN: 1461872 Hom.: 15 Cov.: 32 AF XY: 0.00431 AC XY: 3133 AN XY: 727240

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.00141 AC: 63 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00474 AC: 124 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.00234 AC: 125 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00516 AC: 5734 AN: 1112004

Other (OTH) AF: 0.00391 AC: 236 AN: 60394

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152286 Hom.: 3 Cov.: 32 AF XY: 0.00305 AC XY: 227 AN XY: 74470

African (AFR) AF: 0.000698 AC: 29 AN: 41564

American (AMR) AF: 0.000850 AC: 13 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00538 AC: 366 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00385 Hom.: 1

Bravo AF: 0.00274

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.9
DANN	Benign	0.85
PhyloP100		0.020
PromoterAI		-0.020	Neutral
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2404579; hg19: chr16-4558064;