2-200929450-A-T

Variant names:

• chr2-200929450-A-T
• rs9288314
• NM_006190.5:c.917+1889T>A

Variant summary

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

The NM_006190.5(ORC2):​c.917+1889T>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 152,122 control chromosomes in the GnomAD database, including 4,379 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 (4379 hom., cov: 31)
• Consequence: ORC2 NM_006190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC2	NM_006190.5	c.917+1889T>A		intron_variant	Intron 11 of 17	ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7	c.917+1889T>A		intron_variant	Intron 11 of 17	1	NM_006190.5	ENSP00000234296.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32750 AN: 152004 Hom.: 4371 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.216 AC: 32799 AN: 152122 Hom.: 4379 Cov.: 31 AF XY: 0.211 AC XY: 15706 AN XY: 74376

African (AFR) AF: 0.372 AC: 15396 AN: 41434

American (AMR) AF: 0.161 AC: 2454 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3472

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5184

South Asian (SAS) AF: 0.0686 AC: 331 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11485 AN: 68004

Other (OTH) AF: 0.203 AC: 430 AN: 2114

Alfa AF: 0.201 Hom.: 472

Bravo AF: 0.225

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	-0.92
CADD	Benign	2.5
DANN	Benign	0.53
PhyloP100		0.14
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: rs9288314; hg19: chr2-201794173;