rs4622700

Variant names:

• chr2-200928390-C-T
• rs4622700
• NM_006190.5:c.918-1490G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006190.5(ORC2):​c.918-1490G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,888 control chromosomes in the GnomAD database, including 4,382 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 0.22 (4382 hom., cov: 31)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006190.5. 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
	ORC2	NM_006190.5	MANE Select	c.918-1490G>A		intron	N/A	NP_006181.1	Q13416
	ORC2	NR_033915.2		n.1148-1490G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	ENST00000234296.7	TSL:1 MANE Select	c.918-1490G>A		intron	N/A	ENSP00000234296.2	Q13416
	ORC2	ENST00000938732.1		c.978-1490G>A		intron	N/A	ENSP00000608791.1
	ORC2	ENST00000879137.1		c.963-1490G>A		intron	N/A	ENSP00000549196.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32721 AN: 151770 Hom.: 4374 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00850

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32770 AN: 151888 Hom.: 4382 Cov.: 31 AF XY: 0.211 AC XY: 15678 AN XY: 74230

African (AFR) AF: 0.372 AC: 15393 AN: 41398

American (AMR) AF: 0.160 AC: 2447 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 750 AN: 3464

East Asian (EAS) AF: 0.00852 AC: 44 AN: 5162

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4818

European-Finnish (FIN) AF: 0.164 AC: 1725 AN: 10542

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11478 AN: 67926

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.188 Hom.: 1805

Bravo AF: 0.225

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.40
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs4622700; hg19: chr2-201793113;