2-10441508-C-CCA

Position:

• chr2-10441508-C-CCA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000234111.9(ODC1):​c.1241_1241+1insTG​(p.Trp414CysfsTer17) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ODC1 ENST00000234111.9 frameshift, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.50

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-10441508-C-CCA is Pathogenic according to our data. Variant chr2-10441508-C-CCA is described in ClinVar as [Pathogenic]. Clinvar id is 983286.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODC1	NM_002539.3	c.1241_1241+1insTG	p.Trp414CysfsTer17	frameshift_variant, splice_region_variant		ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2	c.854_854+1insTG	p.Trp285CysfsTer17	frameshift_variant, splice_region_variant			NP_001274117.1
ODC1	NM_001287189.2	c.1241_1241+1insTG	p.Trp414CysfsTer17	frameshift_variant, splice_region_variant			NP_001274118.1
ODC1	NM_001287190.2	c.1241_1241+1insTG	p.Trp414CysfsTer17	frameshift_variant, splice_region_variant			NP_001274119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.1241_1241+1insTG	p.Trp414CysfsTer17	frameshift_variant, splice_region_variant		1	NM_002539.3	ENSP00000234111	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with alopecia and brain abnormalities Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1671814787; hg19: chr2-10581634;