rs11894842

Variant names:

• chr2-200908822-T-C
• rs11894842
• NM_006190.5:c.*2479A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-200908822-T-C
• chr2-200908822-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006190.5(ORC2):​c.*2479A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,722 control chromosomes in the GnomAD database, including 10,002 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 0.32 (10002 hom., cov: 30)
• Consequence: ORC2 NM_006190.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC2	NM_006190.5	c.*2479A>G		downstream_gene_variant		ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7	c.*2479A>G		downstream_gene_variant		1	NM_006190.5	ENSP00000234296.2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47848 AN: 151602 Hom.: 9976 Cov.: 30

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.316 AC: 47932 AN: 151722 Hom.: 10002 Cov.: 30 AF XY: 0.311 AC XY: 23030 AN XY: 74120

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.291

Alfa AF: 0.240 Hom.: 5336

Bravo AF: 0.327

Asia WGS AF: 0.140 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11894842; hg19: chr2-201773545;