2-10440737-C-G

Variant names:

• chr2-10440737-C-G
• NM_002539.3:c.1373G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002539.3(ODC1):​c.1373G>C​(p.Ser458Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODC1 NM_002539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19
• Publications: 0 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)

ENSG00000298698 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1380617).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	NM_002539.3	MANE Select	c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	NP_002530.1	P11926
	ODC1	NM_001287189.2		c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	NP_001274118.1	P11926
	ODC1	NM_001287190.2		c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	NP_001274119.1	P11926

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	ENSP00000234111.4	P11926
	ODC1	ENST00000405333.5	TSL:2	c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	ENSP00000385333.1	P11926
	ODC1	ENST00000443218.2	TSL:2	c.1373G>C	p.Ser458Thr	missense	Exon 12 of 12	ENSP00000390691.2	P11926

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.083
Sift	Benign	0.15	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.23		Gain of sheet (P = 0.0344)
MVP		0.33
MPC		0.36
ClinPred		0.48	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.42
Mutation Taster		=83/17	polymorphism

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

hg19: chr2-10580863;