chr2-200959369-G-A

Position:

• chr2-200959369-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
ORC2	NM_006190.5	c.-11+23C>T		intron_variant		ENST00000234296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC2	ENST00000234296.7	c.-11+23C>T		intron_variant		1	NM_006190.5	P1
ORC2	ENST00000410039.5	c.-11+23C>T		intron_variant		5
ORC2	ENST00000457595.1	c.-11+23C>T		intron_variant		2
ORC2	ENST00000467605.5	n.240+23C>T		intron_variant, non_coding_transcript_variant		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

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

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.219

Alfa AF: 0.164 Hom.: 1058

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

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: rs2307357; hg19: chr2-201824092;