2-200909632-T-C

Position:

• chr2-200909632-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.*1669A>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 0.339 in 142,300 control chromosomes in the GnomAD database, including 10,543 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 0.34 (10542 hom., cov: 25)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: ORC2 NM_006190.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC2	NM_006190.5	c.*1669A>G		3_prime_UTR_variant	18/18	ENST00000234296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC2	ENST00000234296.7	c.*1669A>G		3_prime_UTR_variant	18/18	1	NM_006190.5	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 48171 AN: 142162 Hom.: 10513 Cov.: 25

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.222 AC: 8 AN: 36 Hom.: 1 Cov.: 0 AF XY: 0.154 AC XY: 4 AN XY: 26

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.233

GnomAD4 genome AF: 0.339 AC: 48263 AN: 142264 Hom.: 10542 Cov.: 25 AF XY: 0.339 AC XY: 23120 AN XY: 68148

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.314

Alfa AF: 0.130 Hom.: 213

Bravo AF: 0.337

Asia WGS AF: 0.144 AC: 501 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.20

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: rs13412430; hg19: chr2-201774355;