rs2307358

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-200920934-T-A
• chr2-200920934-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006190.5(ORC2):​c.1294+59A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,231,736 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.1294+59A>T		intron	N/A	NP_006181.1
	ORC2	NR_033915.2		n.1524+59A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	ENST00000234296.7	TSL:1 MANE Select	c.1294+59A>T		intron	N/A	ENSP00000234296.2
	ORC2	ENST00000938732.1		c.1354+59A>T		intron	N/A	ENSP00000608791.1
	ORC2	ENST00000879137.1		c.1339+59A>T		intron	N/A	ENSP00000549196.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1079698 Hom.: 0 AF XY: 0.00000189 AC XY: 1 AN XY: 529026

African (AFR) AF: 0.00 AC: 0 AN: 22744

American (AMR) AF: 0.00 AC: 0 AN: 20620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17252

East Asian (EAS) AF: 0.0000324 AC: 1 AN: 30896

South Asian (SAS) AF: 0.00 AC: 0 AN: 36160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 860950

Other (OTH) AF: 0.00 AC: 0 AN: 44358

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.34
PhyloP100		-2.1

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: rs2307358; hg19: chr2-201785657;