2-200951698-T-A

Position:

• chr2-200951698-T-A

Variant summary

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

The NM_006190.5(ORC2):​c.239-2055A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,210 control chromosomes in the GnomAD database, including 2,368 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 0.17 (2368 hom., cov: 32)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC2	NM_006190.5	c.239-2055A>T		intron_variant		ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7	c.239-2055A>T		intron_variant		1	NM_006190.5	ENSP00000234296	P1
ORC2	ENST00000410039.5	c.239-2055A>T		intron_variant		5		ENSP00000386390
ORC2	ENST00000467605.5	n.385-2055A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25608 AN: 152092 Hom.: 2363 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.168 AC: 25633 AN: 152210 Hom.: 2368 Cov.: 32 AF XY: 0.165 AC XY: 12295 AN XY: 74424

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.0687

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.173

Alfa AF: 0.174 Hom.: 312

Bravo AF: 0.171

Asia WGS AF: 0.0560 AC: 195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.097

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: rs13392371; hg19: chr2-201816421;