Genetic Variant ORC2:c.*1669A>G (chr2-200909632-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.*1669A>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 0.339 in 142,300 control chromosomes in the GnomAD database, including 10,543 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 0.34 ( 10542 hom., cov: 25)

Exomes 𝑓: 0.22 ( 1 hom. )

Consequence

ORC2
NM_006190.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

8 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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC2	NM_006190.5 link	c.*1669A>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000234296.7	NP_006181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC2	ENST00000234296.7 link	c.*1669A>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_006190.5	ENSP00000234296.2
ENSG00000308129	ENST00000831870.1 link	n.221+2159A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

48171

AN:

142162

Hom.:

10513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.0136

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.222

AC:

AN:

Hom.:

Cov.:

AF XY:

0.154

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)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.233

AC:

AN:

Other (OTH)

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.339

AC:

48263

AN:

142264

Hom.:

10542

Cov.:

AF XY:

0.339

AC XY:

23120

AN XY:

68148

show subpopulations

African (AFR)

AF:

0.637

AC:

25075

AN:

39366

American (AMR)

AF:

0.247

AC:

3140

AN:

12714

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1167

AN:

3422

East Asian (EAS)

AF:

0.0137

AC:

AN:

4678

South Asian (SAS)

AF:

0.160

AC:

714

AN:

4456

European-Finnish (FIN)

AF:

0.242

AC:

2053

AN:

8490

Middle Eastern (MID)

AF:

0.265

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.230

AC:

15200

AN:

66050

Other (OTH)

AF:

0.314

AC:

609

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.130

Hom.:

213

Bravo

AF:

0.337

Asia WGS

AF:

0.144

AC:

501

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.84

(source)

DANN

Benign

0.20

PhyloP100

-0.28

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over