2-200963642-C-G

Variant names:

• chr2-200963642-C-G
• rs3087357
• NM_006190.5:c.-212G>C

Variant summary

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

The NM_006190.5(ORC2):​c.-212G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 398,346 control chromosomes in the GnomAD database, including 8,968 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 0.23 (4725 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4243 hom.)
• Consequence: ORC2 NM_006190.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 17 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]

ENSG00000183308 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 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.-212G>C		5_prime_UTR	Exon 1 of 18	NP_006181.1	Q13416
	ORC2	NR_033915.2		n.19G>C		non_coding_transcript_exon	Exon 1 of 17
	LOC105373835	NR_187975.1		n.199+12C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	ENST00000234296.7	TSL:1 MANE Select	c.-212G>C		5_prime_UTR	Exon 1 of 18	ENSP00000234296.2	Q13416
	ORC2	ENST00000938732.1		c.-212G>C		5_prime_UTR	Exon 1 of 19	ENSP00000608791.1
	ORC2	ENST00000879137.1		c.-212G>C		5_prime_UTR	Exon 1 of 19	ENSP00000549196.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34555 AN: 152072 Hom.: 4718 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00888

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.175 AC: 42957 AN: 246156 Hom.: 4243 Cov.: 0 AF XY: 0.175 AC XY: 21799 AN XY: 124804

African (AFR) AF: 0.368 AC: 2641 AN: 7170

American (AMR) AF: 0.149 AC: 1102 AN: 7420

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 2120 AN: 9226

East Asian (EAS) AF: 0.00232 AC: 53 AN: 22882

South Asian (SAS) AF: 0.0884 AC: 265 AN: 2998

European-Finnish (FIN) AF: 0.186 AC: 3879 AN: 20806

Middle Eastern (MID) AF: 0.170 AC: 220 AN: 1294

European-Non Finnish (NFE) AF: 0.187 AC: 29550 AN: 157996

Other (OTH) AF: 0.191 AC: 3127 AN: 16364

GnomAD4 genome AF: 0.227 AC: 34598 AN: 152190 Hom.: 4725 Cov.: 32 AF XY: 0.223 AC XY: 16559 AN XY: 74412

African (AFR) AF: 0.375 AC: 15571 AN: 41512

American (AMR) AF: 0.168 AC: 2577 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3470

East Asian (EAS) AF: 0.00890 AC: 46 AN: 5170

South Asian (SAS) AF: 0.0807 AC: 389 AN: 4820

European-Finnish (FIN) AF: 0.181 AC: 1917 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12622 AN: 68008

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.0930 Hom.: 118

Bravo AF: 0.235

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		-1.1
PromoterAI		-0.035	Neutral
Mutation Taster		=300/0	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: rs3087357; hg19: chr2-201828365;