rs1049500

Variant names:

• chr2-10440841-G-A
• rs1049500
• NM_002539.3:c.1269C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-10440841-G-A
• chr2-10440841-G-C
• chr2-10440841-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002539.3(ODC1):​c.1269C>T​(p.Pro423Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,613,840 control chromosomes in the GnomAD database, including 13,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2481 hom., cov: 32)
  • Exomes 𝑓: 0.075 (11340 hom.)
• Consequence: ODC1 NM_002539.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.41
• Publications: 18 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-10440841-G-A is Benign according to our data. Variant chr2-10440841-G-A is described in ClinVar as Benign. ClinVar VariationId is 1280616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

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.1269C>T	p.Pro423Pro	synonymous	Exon 12 of 12	NP_002530.1	P11926
	ODC1	NM_001287189.2		c.1269C>T	p.Pro423Pro	synonymous	Exon 12 of 12	NP_001274118.1	P11926
	ODC1	NM_001287190.2		c.1269C>T	p.Pro423Pro	synonymous	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.1269C>T	p.Pro423Pro	synonymous	Exon 12 of 12	ENSP00000234111.4	P11926
	ODC1	ENST00000405333.5	TSL:2	c.1269C>T	p.Pro423Pro	synonymous	Exon 12 of 12	ENSP00000385333.1	P11926
	ODC1	ENST00000443218.2	TSL:2	c.1269C>T	p.Pro423Pro	synonymous	Exon 12 of 12	ENSP00000390691.2	P11926

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20464 AN: 151928 Hom.: 2477 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.135 AC: 34020 AN: 251400 AF XY: 0.132

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.0461

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0421

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0748 AC: 109383 AN: 1461794 Hom.: 11340 Cov.: 31 AF XY: 0.0779 AC XY: 56668 AN XY: 727194

African (AFR) AF: 0.255 AC: 8549 AN: 33478

American (AMR) AF: 0.133 AC: 5958 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 1214 AN: 26136

East Asian (EAS) AF: 0.546 AC: 21672 AN: 39694

South Asian (SAS) AF: 0.213 AC: 18394 AN: 86246

European-Finnish (FIN) AF: 0.112 AC: 6004 AN: 53414

Middle Eastern (MID) AF: 0.0772 AC: 444 AN: 5754

European-Non Finnish (NFE) AF: 0.0370 AC: 41103 AN: 1111972

Other (OTH) AF: 0.100 AC: 6045 AN: 60384

GnomAD4 genome AF: 0.135 AC: 20497 AN: 152046 Hom.: 2481 Cov.: 32 AF XY: 0.142 AC XY: 10574 AN XY: 74316

African (AFR) AF: 0.250 AC: 10340 AN: 41442

American (AMR) AF: 0.122 AC: 1862 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3466

East Asian (EAS) AF: 0.541 AC: 2799 AN: 5172

South Asian (SAS) AF: 0.233 AC: 1120 AN: 4806

European-Finnish (FIN) AF: 0.121 AC: 1281 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2670 AN: 67990

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.0735 Hom.: 3901

Bravo AF: 0.140

Asia WGS AF: 0.357 AC: 1241 AN: 3478

EpiCase AF: 0.0398

EpiControl AF: 0.0406

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		-2.4
Mutation Taster		=99/1	polymorphism (auto)

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: rs1049500; hg19: chr2-10580967; COSMIC: COSV52171477; COSMIC: COSV52171477;