chr2-10440724-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_002539.3(ODC1):​c.1386G>C​(p.Ter462Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ODC1
NM_002539.3 stop_lost

Scores

2
1
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_002539.3 Downstream stopcodon found after 90 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ODC1NM_002539.3 linkc.1386G>C p.Ter462Tyrext*? stop_lost Exon 12 of 12 ENST00000234111.9 NP_002530.1 P11926
ODC1NM_001287189.2 linkc.1386G>C p.Ter462Tyrext*? stop_lost Exon 12 of 12 NP_001274118.1 P11926
ODC1NM_001287190.2 linkc.1386G>C p.Ter462Tyrext*? stop_lost Exon 12 of 12 NP_001274119.1 P11926
ODC1NM_001287188.2 linkc.999G>C p.Ter333Tyrext*? stop_lost Exon 12 of 12 NP_001274117.1 B4DXF8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ODC1ENST00000234111.9 linkc.1386G>C p.Ter462Tyrext*? stop_lost Exon 12 of 12 1 NM_002539.3 ENSP00000234111.4 P11926

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461400
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Oct 30, 2023
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Stop codon loss and change to a tyrosine codon, leading to protein extension and the addition of 5 amino acids at the C-terminus; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
15
DANN
Benign
0.82
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.95
D
Vest4
0.082
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-10580850; API