Variant chr2-200921114-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006190.5(ORC2):c.1173C>T(p.Leu391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,592,800 control chromosomes in the GnomAD database, including 24,732 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 ( 4389 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20343 hom. )

Consequence

ORC2
NM_006190.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Variant links:

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]

ORC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=0.115 with no splicing effect.

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/exons	MANE	Protein	UniProt
ORC2	NM_006190.5 linkuse as main transcript	c.1173C>T	p.Leu391=	synonymous_variant	14/18	ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ORC2	ENST00000234296.7 linkuse as main transcript	c.1173C>T	p.Leu391=	synonymous_variant	14/18	1	NM_006190.5	ENSP00000234296	P1
ORC2	ENST00000464147.1 linkuse as main transcript	n.260C>T		non_coding_transcript_exon_variant	3/6	5
ORC2	ENST00000487853.1 linkuse as main transcript	n.625C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32783

AN:

151916

Hom.:

4381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.371

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.0690

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.154

AC:

37679

AN:

244142

Hom.:

3764

AF XY:

0.150

AC XY:

19839

AN XY:

132050

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.00570

Gnomad SAS exome

AF:

0.0784

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.169

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.160

AC:

230199

AN:

1440766

Hom.:

20343

Cov.:

AF XY:

0.158

AC XY:

113000

AN XY:

717300

show subpopulations

Gnomad4 AFR exome

AF:

0.376

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.00342

Gnomad4 SAS exome

AF:

0.0770

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.216

AC:

32832

AN:

152034

Hom.:

4389

Cov.:

AF XY:

0.211

AC XY:

15713

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.372

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.00849

Gnomad4 SAS

AF:

0.0691

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.159

Hom.:

1010

Bravo

AF:

0.226

Asia WGS

AF:

0.0700

AC:

243

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.6

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over