chr2-200951534-C-T

Position:

• chr2-200951534-C-T

Variant summary

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

The NM_006190.5(ORC2):​c.239-1891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,966 control chromosomes in the GnomAD database, including 4,401 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 0.22 (4401 hom., cov: 32)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC2	NM_006190.5	c.239-1891G>A		intron_variant		ENST00000234296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC2	ENST00000234296.7	c.239-1891G>A		intron_variant		1	NM_006190.5	P1
ORC2	ENST00000410039.5	c.239-1891G>A		intron_variant		5
ORC2	ENST00000467605.5	n.385-1891G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32812 AN: 151848 Hom.: 4393 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.216 AC: 32861 AN: 151966 Hom.: 4401 Cov.: 32 AF XY: 0.212 AC XY: 15740 AN XY: 74278

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.206

Alfa AF: 0.210 Hom.: 657

Bravo AF: 0.226

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.66
DANN	Benign	0.58

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: rs13429609; hg19: chr2-201816257;