2-10446654-T-C

Position:

• chr2-10446654-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.-127-1390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 307,362 control chromosomes in the GnomAD database, including 1,796 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 (806 hom., cov: 33)
  • Exomes 𝑓: 0.10 (990 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.86).
• 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	UniProt
ODC1	NM_002539.3	c.-127-1390A>G		intron_variant		ENST00000234111.9
ODC1	NM_001287188.2	c.-414-1390A>G		intron_variant
ODC1	NM_001287189.2	c.-128+820A>G		intron_variant
ODC1	NM_001287190.2	c.-128+974A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODC1	ENST00000234111.9	c.-127-1390A>G		intron_variant		1	NM_002539.3	P1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13864 AN: 152174 Hom.: 806 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.0899

GnomAD4 exome AF: 0.0999 AC: 15489 AN: 155070 Hom.: 990 AF XY: 0.0993 AC XY: 9300 AN XY: 93674

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.0945

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0956

Gnomad4 NFE exome AF: 0.0916

Gnomad4 OTH exome AF: 0.0949

GnomAD4 genome AF: 0.0911 AC: 13872 AN: 152292 Hom.: 806 Cov.: 33 AF XY: 0.0939 AC XY: 6988 AN XY: 74450

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.0858

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0913

Alfa AF: 0.0861 Hom.: 106

Bravo AF: 0.0995

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.49

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: rs28362380; hg19: chr2-10586780;