chr2-10440781-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_002539.3(ODC1):​c.1329G>A​(p.Trp443*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ODC1
NM_002539.3 stop_gained

Scores

3
3
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.74
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 Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0411 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-10440781-C-T is Pathogenic according to our data. Variant chr2-10440781-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3776026.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ODC1NM_002539.3 linkc.1329G>A p.Trp443* stop_gained Exon 12 of 12 ENST00000234111.9 NP_002530.1 P11926
ODC1NM_001287189.2 linkc.1329G>A p.Trp443* stop_gained Exon 12 of 12 NP_001274118.1 P11926
ODC1NM_001287190.2 linkc.1329G>A p.Trp443* stop_gained Exon 12 of 12 NP_001274119.1 P11926
ODC1NM_001287188.2 linkc.942G>A p.Trp314* stop_gained Exon 12 of 12 NP_001274117.1 B4DXF8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ODC1ENST00000234111.9 linkc.1329G>A p.Trp443* stop_gained Exon 12 of 12 1 NM_002539.3 ENSP00000234111.4 P11926

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with alopecia and brain abnormalities Pathogenic:1
Jul 20, 2023
3billion
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.52
D
BayesDel_noAF
Pathogenic
0.50
CADD
Pathogenic
38
DANN
Uncertain
0.99
Eigen
Pathogenic
0.78
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.92
D
Vest4
0.64
ClinPred
0.99
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: chr2-10580907; API