rs13412214

Positions:

• chr2-200909459-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006190.5(ORC2):​c.*1842A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,886 control chromosomes in the GnomAD database, including 10,823 homozygotes. 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: 𝑓 0.33 (10823 hom., cov: 30)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: ORC2 NM_006190.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

Genes affected

ORC2 (HGNC:8488): (origin recognition complex subunit 2) The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. This protein forms a core complex with ORC3, -4, and -5. It also interacts with CDC45 and MCM10, which are proteins known to be important for the initiation of DNA replication. This protein has been demonstrated to specifically associate with the origin of replication of Epstein-Barr virus in human cells, and is thought to be required for DNA replication from viral origin of replication. Alternatively spliced transcript variants have been found, one of which is a nonsense-mediated mRNA decay candidate. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC2	NM_006190.5	c.*1842A>G		3_prime_UTR_variant	18/18	ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7	c.*1842A>G		3_prime_UTR_variant	18/18	1	NM_006190.5	ENSP00000234296	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49267 AN: 151752 Hom.: 10794 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.325 AC: 49359 AN: 151870 Hom.: 10823 Cov.: 30 AF XY: 0.319 AC XY: 23703 AN XY: 74260

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.298

Alfa AF: 0.293 Hom.: 1045

Bravo AF: 0.337

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs13412214; hg19: chr2-201774182;