chr2-10446534-A-G

Variant names:

• chr2-10446534-A-G
• rs12616336
• NM_002539.3:c.-127-1270T>C

Variant summary

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

The NM_002539.3(ODC1):​c.-127-1270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,322 control chromosomes in the GnomAD database, including 429 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 0.067 (429 hom., cov: 33)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 2 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]

SNORA80B (HGNC:34355): (small nucleolar RNA, H/ACA box 80B)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0889 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	NM_002539.3	MANE Select	c.-127-1270T>C		intron	N/A	NP_002530.1
	ODC1	NM_001287189.2		c.-128+940T>C		intron	N/A	NP_001274118.1
	ODC1	NM_001287190.2		c.-128+1094T>C		intron	N/A	NP_001274119.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.-127-1270T>C		intron	N/A	ENSP00000234111.4
	ODC1	ENST00000405333.5	TSL:2	c.-128+940T>C		intron	N/A	ENSP00000385333.1
	ODC1	ENST00000443218.2	TSL:2	c.-128+1094T>C		intron	N/A	ENSP00000390691.2

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10171 AN: 152204 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0668 AC: 10169 AN: 152322 Hom.: 429 Cov.: 33 AF XY: 0.0674 AC XY: 5016 AN XY: 74474

African (AFR) AF: 0.0170 AC: 705 AN: 41580

American (AMR) AF: 0.0836 AC: 1280 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3472

East Asian (EAS) AF: 0.0441 AC: 229 AN: 5188

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4830

European-Finnish (FIN) AF: 0.0882 AC: 935 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0908 AC: 6177 AN: 68028

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0808 Hom.: 185

Bravo AF: 0.0654

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12616336; hg19: chr2-10586660;