rs2302615

Variant names:

• chr2-10448012-C-T
• rs2302615
• NM_002539.3:c.-128+109G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001287189.2(ODC1):​c.-666G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 153,462 control chromosomes in the GnomAD database, including 7,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7859 hom., cov: 35)
  • Exomes 𝑓: 0.29 (68 hom.)
• Consequence: ODC1 NM_001287189.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.370
• Publications: 19 publications found

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]

ODC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with alopecia and brain abnormalities

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-10448012-C-T is Benign according to our data. Variant chr2-10448012-C-T is described in ClinVar as Benign. ClinVar VariationId is 13806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287189.2. 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
	ODC1	NM_002539.3	MANE Select	c.-128+109G>A		intron	N/A	NP_002530.1	P11926
	ODC1	NM_001287189.2		c.-666G>A		5_prime_UTR	Exon 1 of 12	NP_001274118.1	P11926
	ODC1	NM_001287190.2		c.-512G>A		5_prime_UTR	Exon 1 of 12	NP_001274119.1	P11926

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.-128+109G>A		intron	N/A	ENSP00000234111.4	P11926
	ODC1	ENST00000443218.2	TSL:2	c.-512G>A		5_prime_UTR	Exon 1 of 12	ENSP00000390691.2	P11926
	ODC1	ENST00000887506.1		c.-516G>A		5_prime_UTR	Exon 1 of 12	ENSP00000557565.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47412 AN: 151864 Hom.: 7856 Cov.: 35

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.291 AC: 433 AN: 1490 Hom.: 68 AF XY: 0.280 AC XY: 246 AN XY: 880

African (AFR) AF: 0.333 AC: 14 AN: 42

American (AMR) AF: 0.271 AC: 13 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 9 AN: 38

East Asian (EAS) AF: 0.688 AC: 33 AN: 48

South Asian (SAS) AF: 0.300 AC: 3 AN: 10

European-Finnish (FIN) AF: 0.359 AC: 69 AN: 192

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.259 AC: 262 AN: 1010

Other (OTH) AF: 0.293 AC: 27 AN: 92

GnomAD4 genome AF: 0.312 AC: 47454 AN: 151972 Hom.: 7859 Cov.: 35 AF XY: 0.322 AC XY: 23910 AN XY: 74308

African (AFR) AF: 0.376 AC: 15607 AN: 41482

American (AMR) AF: 0.262 AC: 4001 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2882 AN: 5134

South Asian (SAS) AF: 0.421 AC: 2034 AN: 4832

European-Finnish (FIN) AF: 0.390 AC: 4122 AN: 10556

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17233 AN: 67904

Other (OTH) AF: 0.292 AC: 617 AN: 2112

Alfa AF: 0.294 Hom.: 816

Bravo AF: 0.307

Asia WGS AF: 0.471 AC: 1624 AN: 3450

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Ornithine decarboxylase 1 polymorphism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		0.37
PromoterAI		-0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2302615; hg19: chr2-10588138;