chr2-10445185-A-C

Variant names:

• chr2-10445185-A-C
• rs2302614
• NM_002539.3:c.-48T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002539.3(ODC1):​c.-48T>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 0.116 in 574,910 control chromosomes in the GnomAD database, including 8,751 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 0.13 (2310 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6441 hom.)
• Consequence: ODC1 NM_002539.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-48T>G		5_prime_UTR_variant	Exon 2 of 12	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.-48T>G		5_prime_UTR_variant	Exon 2 of 12		NP_001274118.1
ODC1	NM_001287190.2	c.-48T>G		5_prime_UTR_variant	Exon 2 of 12		NP_001274119.1
ODC1	NM_001287188.2	c.-335T>G		5_prime_UTR_variant	Exon 2 of 12		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-48T>G		5_prime_UTR_variant	Exon 2 of 12	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19789 AN: 152144 Hom.: 2306 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.111 AC: 46737 AN: 422648 Hom.: 6441 Cov.: 4 AF XY: 0.114 AC XY: 25566 AN XY: 224534

African (AFR) AF: 0.235 AC: 2741 AN: 11640

American (AMR) AF: 0.124 AC: 2201 AN: 17798

Ashkenazi Jewish (ASJ) AF: 0.0492 AC: 636 AN: 12916

East Asian (EAS) AF: 0.547 AC: 15459 AN: 28286

South Asian (SAS) AF: 0.214 AC: 9464 AN: 44252

European-Finnish (FIN) AF: 0.109 AC: 2923 AN: 26746

Middle Eastern (MID) AF: 0.0685 AC: 135 AN: 1972

European-Non Finnish (NFE) AF: 0.0416 AC: 10612 AN: 255006

Other (OTH) AF: 0.107 AC: 2566 AN: 24032

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152262 Hom.: 2310 Cov.: 33 AF XY: 0.138 AC XY: 10283 AN XY: 74454

African (AFR) AF: 0.233 AC: 9672 AN: 41516

American (AMR) AF: 0.121 AC: 1851 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2782 AN: 5182

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4830

European-Finnish (FIN) AF: 0.121 AC: 1284 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2678 AN: 68030

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0461 Hom.: 92

Bravo AF: 0.135

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.87
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2302614; hg19: chr2-10585311;