2-200920934-T-C

Variant names:

• chr2-200920934-T-C
• rs2307358
• NM_006190.5:c.1294+59A>G

Variant summary

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

The NM_006190.5(ORC2):​c.1294+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,229,952 control chromosomes in the GnomAD database, including 19,914 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 (4411 hom., cov: 32)
  • Exomes 𝑓: 0.16 (15503 hom.)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 14 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=-0.87).
• 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.1294+59A>G		intron	N/A	NP_006181.1	Q13416
	ORC2	NR_033915.2		n.1524+59A>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.1294+59A>G		intron	N/A	ENSP00000234296.2	Q13416
	ORC2	ENST00000938732.1		c.1354+59A>G		intron	N/A	ENSP00000608791.1
	ORC2	ENST00000879137.1		c.1339+59A>G		intron	N/A	ENSP00000549196.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32840 AN: 151982 Hom.: 4403 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.163 AC: 175362 AN: 1077852 Hom.: 15503 AF XY: 0.161 AC XY: 85208 AN XY: 528106

African (AFR) AF: 0.379 AC: 8616 AN: 22706

American (AMR) AF: 0.120 AC: 2474 AN: 20604

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 3667 AN: 17222

East Asian (EAS) AF: 0.00288 AC: 89 AN: 30894

South Asian (SAS) AF: 0.0740 AC: 2672 AN: 36118

European-Finnish (FIN) AF: 0.171 AC: 7198 AN: 42110

Middle Eastern (MID) AF: 0.160 AC: 730 AN: 4562

European-Non Finnish (NFE) AF: 0.166 AC: 142612 AN: 859334

Other (OTH) AF: 0.165 AC: 7304 AN: 44302

GnomAD4 genome AF: 0.216 AC: 32889 AN: 152100 Hom.: 4411 Cov.: 32 AF XY: 0.212 AC XY: 15751 AN XY: 74372

African (AFR) AF: 0.372 AC: 15429 AN: 41464

American (AMR) AF: 0.163 AC: 2482 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5182

South Asian (SAS) AF: 0.0688 AC: 331 AN: 4812

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10574

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11505 AN: 68010

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.195 Hom.: 778

Bravo AF: 0.226

Asia WGS AF: 0.0690 AC: 242 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.31
PhyloP100		-2.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2307358;

hg19: chr2-201785657;