rs2302613

Positions:

• chr2-10445176-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002539.3(ODC1):​c.-39A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 590,594 control chromosomes in the GnomAD database, including 3,535 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 0.091 (822 hom., cov: 33)
  • Exomes 𝑓: 0.10 (2713 hom.)
• Consequence: ODC1 NM_002539.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

Genes affected

ODC1 (HGNC:8109): (ornithine decarboxylase 1) This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. The activity level for the enzyme varies in response to growth-promoting stimuli and exhibits a high turnover rate in comparison to other mammalian proteins. Originally localized to both chromosomes 2 and 7, the gene encoding this enzyme has been determined to be located on 2p25, with a pseudogene located on 7q31-qter. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-39A>G		5_prime_UTR_variant	2/12	ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2	c.-326A>G		5_prime_UTR_variant	2/12		NP_001274117.1
ODC1	NM_001287189.2	c.-39A>G		5_prime_UTR_variant	2/12		NP_001274118.1
ODC1	NM_001287190.2	c.-39A>G		5_prime_UTR_variant	2/12		NP_001274119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-39A>G		5_prime_UTR_variant	2/12	1	NM_002539.3	ENSP00000234111	P1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13880 AN: 152142 Hom.: 822 Cov.: 33

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0889

GnomAD4 exome AF: 0.102 AC: 44858 AN: 438334 Hom.: 2713 Cov.: 5 AF XY: 0.102 AC XY: 23747 AN XY: 232854

Gnomad4 AFR exome AF: 0.0444

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.0852

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0896

Gnomad4 NFE exome AF: 0.0913

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0912 AC: 13888 AN: 152260 Hom.: 822 Cov.: 33 AF XY: 0.0940 AC XY: 6999 AN XY: 74434

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0899 Hom.: 163

Bravo AF: 0.0995

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2302613; hg19: chr2-10585302; COSMIC: COSV52172916; COSMIC: COSV52172916;