chr2-10448065-C-A

Variant names:

• chr2-10448065-C-A
• rs2302616
• NM_002539.3:c.-128+56G>T

Variant summary

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

The NM_002539.3(ODC1):​c.-128+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 158,658 control chromosomes in the GnomAD database, including 6,082 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 0.26 (5726 hom., cov: 35)
  • Exomes 𝑓: 0.31 (356 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002539.3. 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+56G>T		intron	N/A	NP_002530.1
	ODC1	NM_001287188.2		c.-415+56G>T		intron	N/A	NP_001274117.1
	ODC1	NM_001287189.2		c.-719G>T		upstream_gene	N/A	NP_001274118.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.-128+56G>T		intron	N/A	ENSP00000234111.4
	ODC1	ENST00000699836.1		c.-18+56G>T		intron	N/A	ENSP00000514634.1
	ODC1	ENST00000887501.1		c.-128+1703G>T		intron	N/A	ENSP00000557560.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38783 AN: 151784 Hom.: 5727 Cov.: 35

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.308 AC: 2085 AN: 6768 Hom.: 356 AF XY: 0.308 AC XY: 1213 AN XY: 3938

African (AFR) AF: 0.169 AC: 22 AN: 130

American (AMR) AF: 0.172 AC: 41 AN: 238

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 46 AN: 160

East Asian (EAS) AF: 0.0625 AC: 14 AN: 224

South Asian (SAS) AF: 0.188 AC: 15 AN: 80

European-Finnish (FIN) AF: 0.335 AC: 287 AN: 856

Middle Eastern (MID) AF: 0.261 AC: 12 AN: 46

European-Non Finnish (NFE) AF: 0.332 AC: 1518 AN: 4578

Other (OTH) AF: 0.285 AC: 130 AN: 456

GnomAD4 genome AF: 0.255 AC: 38785 AN: 151890 Hom.: 5726 Cov.: 35 AF XY: 0.251 AC XY: 18606 AN XY: 74268

African (AFR) AF: 0.132 AC: 5490 AN: 41490

American (AMR) AF: 0.202 AC: 3086 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3468

East Asian (EAS) AF: 0.0672 AC: 347 AN: 5164

South Asian (SAS) AF: 0.279 AC: 1350 AN: 4834

European-Finnish (FIN) AF: 0.319 AC: 3354 AN: 10508

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23093 AN: 67854

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.292 Hom.: 861

Bravo AF: 0.237

Asia WGS AF: 0.158 AC: 542 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.5
DANN	Benign	0.73
PhyloP100		-0.47
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		3.5
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: rs2302616; hg19: chr2-10588191;