chr2-200944981-C-T

Variant names:

• chr2-200944981-C-T
• rs10205561
• NM_006190.5:c.329-2204G>A

Variant summary

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

The NM_006190.5(ORC2):​c.329-2204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,122 control chromosomes in the GnomAD database, including 8,303 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 0.28 (8303 hom., cov: 32)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 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.329-2204G>A		intron	N/A	NP_006181.1
	ORC2	NR_033915.2		n.559-2204G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	ENST00000234296.7	TSL:1 MANE Select	c.329-2204G>A		intron	N/A	ENSP00000234296.2
	ORC2	ENST00000467605.5	TSL:3	n.475-2204G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42260 AN: 152004 Hom.: 8289 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.278 AC: 42321 AN: 152122 Hom.: 8303 Cov.: 32 AF XY: 0.273 AC XY: 20307 AN XY: 74374

African (AFR) AF: 0.552 AC: 22912 AN: 41480

American (AMR) AF: 0.186 AC: 2837 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3470

East Asian (EAS) AF: 0.00965 AC: 50 AN: 5182

South Asian (SAS) AF: 0.0813 AC: 392 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1910 AN: 10582

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12647 AN: 67992

Other (OTH) AF: 0.257 AC: 540 AN: 2104

Alfa AF: 0.219 Hom.: 9042

Bravo AF: 0.293

Asia WGS AF: 0.0830 AC: 289 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	1.1
DANN	Benign	0.66
PhyloP100		-0.33
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: rs10205561; hg19: chr2-201809704;