dbSNP rs13412214: ORC2:c.*1842A>G (chr2-200909459-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006190.5(ORC2):c.*1842A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,886 control chromosomes in the GnomAD database, including 10,823 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 0.33 ( 10823 hom., cov: 30)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

ORC2
NM_006190.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.708

Publications

9 publications found

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:

ENSG00000308129 (HGNC:):

ENSG00000308129 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC2	NM_006190.5 link	c.*1842A>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000234296.7	NP_006181.1	Q13416A0A024R411

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7 link	c.*1842A>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_006190.5	ENSP00000234296.2		Q13416
ENSG00000308129	ENST00000831870.1 link	n.221+2332A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49267

AN:

151752

Hom.:

10794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.325

AC:

49359

AN:

151870

Hom.:

10823

Cov.:

AF XY:

0.319

AC XY:

23703

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.624

AC:

25828

AN:

41372

American (AMR)

AF:

0.210

AC:

3209

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1167

AN:

3470

East Asian (EAS)

AF:

0.0126

AC:

AN:

5170

South Asian (SAS)

AF:

0.155

AC:

746

AN:

4818

European-Finnish (FIN)

AF:

0.205

AC:

2164

AN:

10534

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15311

AN:

67926

Other (OTH)

AF:

0.298

AC:

627

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1414

2828

4241

5655

7069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.293

Hom.:

1045

Bravo

AF:

0.337

Asia WGS

AF:

0.145

AC:

507

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

4.0

(source)

DANN

Benign

0.63

PhyloP100

-0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over