chr2-200959369-G-A

Variant names:

• chr2-200959369-G-A
• rs2307357
• NM_006190.5:c.-11+23C>T

Variant summary

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

The NM_006190.5(ORC2):​c.-11+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,144 control chromosomes in the GnomAD database, including 4,713 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 0.23 (4713 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC2	NM_006190.5	c.-11+23C>T		intron_variant	Intron 2 of 17	ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7	c.-11+23C>T		intron_variant	Intron 2 of 17	1	NM_006190.5	ENSP00000234296.2
ORC2	ENST00000410039.5	c.-11+23C>T		intron_variant	Intron 2 of 4	5		ENSP00000386390.1
ORC2	ENST00000457595.1	c.-11+23C>T		intron_variant	Intron 2 of 3	2		ENSP00000396641.1
ORC2	ENST00000467605.5	n.240+23C>T		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34560 AN: 152026 Hom.: 4706 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.227 AC: 34609 AN: 152144 Hom.: 4713 Cov.: 32 AF XY: 0.223 AC XY: 16580 AN XY: 74390

African (AFR) AF: 0.376 AC: 15586 AN: 41480

American (AMR) AF: 0.168 AC: 2573 AN: 15290

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

East Asian (EAS) AF: 0.00887 AC: 46 AN: 5186

South Asian (SAS) AF: 0.0810 AC: 390 AN: 4816

European-Finnish (FIN) AF: 0.181 AC: 1910 AN: 10580

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

European-Non Finnish (NFE) AF: 0.185 AC: 12612 AN: 68002

Other (OTH) AF: 0.219 AC: 463 AN: 2116

Alfa AF: 0.167 Hom.: 1202

Bravo AF: 0.236

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.40
PhyloP100		-0.31
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: rs2307357; hg19: chr2-201824092;