NM_002539.3:c.-48T>A

Variant names:

• chr2-10445185-A-T
• rs2302614
• NM_002539.3:c.-48T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002539.3(ODC1):​c.-48T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODC1 NM_002539.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-48T>A		5_prime_UTR_variant	Exon 2 of 12	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.-48T>A		5_prime_UTR_variant	Exon 2 of 12		NP_001274118.1
ODC1	NM_001287190.2	c.-48T>A		5_prime_UTR_variant	Exon 2 of 12		NP_001274119.1
ODC1	NM_001287188.2	c.-335T>A		5_prime_UTR_variant	Exon 2 of 12		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-48T>A		5_prime_UTR_variant	Exon 2 of 12	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 422972 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 224702

African (AFR) AF: 0.00 AC: 0 AN: 11666

American (AMR) AF: 0.00 AC: 0 AN: 17824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12928

East Asian (EAS) AF: 0.00 AC: 0 AN: 28370

South Asian (SAS) AF: 0.00 AC: 0 AN: 44286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 255100

Other (OTH) AF: 0.00 AC: 0 AN: 24054

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.89
PhyloP100		-1.4

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: rs2302614; hg19: chr2-10585311;