2-200938988-G-A

Variant names:

• chr2-200938988-G-A
• rs10185727
• NM_006190.5:c.454-1022C>T

Variant summary

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

The NM_006190.5(ORC2):​c.454-1022C>T 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 150,854 control chromosomes in the GnomAD database, including 4,360 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 (4360 hom., cov: 30)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	NM_006190.5	MANE Select	c.454-1022C>T		intron	N/A	NP_006181.1
	ORC2	NR_033915.2		n.684-1022C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	ENST00000234296.7	TSL:1 MANE Select	c.454-1022C>T		intron	N/A	ENSP00000234296.2
	ORC2	ENST00000938732.1		c.514-1022C>T		intron	N/A	ENSP00000608791.1
	ORC2	ENST00000879137.1		c.499-1022C>T		intron	N/A	ENSP00000549196.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32527 AN: 150738 Hom.: 4352 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00853

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.125

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: 32576 AN: 150854 Hom.: 4360 Cov.: 30 AF XY: 0.211 AC XY: 15563 AN XY: 73588

African (AFR) AF: 0.373 AC: 15286 AN: 40952

American (AMR) AF: 0.161 AC: 2429 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 747 AN: 3464

East Asian (EAS) AF: 0.00855 AC: 44 AN: 5148

South Asian (SAS) AF: 0.0692 AC: 331 AN: 4780

European-Finnish (FIN) AF: 0.166 AC: 1704 AN: 10290

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.169 AC: 11443 AN: 67812

Other (OTH) AF: 0.202 AC: 422 AN: 2084

Alfa AF: 0.201 Hom.: 472

Bravo AF: 0.225

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		0.75
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: rs10185727; hg19: chr2-201803711;