dbSNP rs11894842: ENSG00000308129:n.221+2969A>G (chr2-200908822-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 ENST00000831870.1(ENSG00000308129):n.221+2969A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,722 control chromosomes in the GnomAD database, including 10,002 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 0.32 ( 10002 hom., cov: 30)

Consequence

ENSG00000308129
ENST00000831870.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.587

Publications

16 publications found

Variant links:

Genes affected

ENSG00000308129 (HGNC:):

ENSG00000308129 links:

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:

Genome browser will be placed here

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=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000831870.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC2	NM_006190.5	MANE Select	c.*2479A>G		downstream_gene	N/A	NP_006181.1	Q13416
	ORC2	NR_033915.2		n.*155A>G		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000308129	ENST00000831870.1		n.221+2969A>G	intron	N/A
ORC2	ENST00000234296.7	TSL:1 MANE Select	c.*2479A>G	downstream_gene	N/A	ENSP00000234296.2	Q13416
ORC2	ENST00000938730.1		c.*2479A>G	downstream_gene	N/A	ENSP00000608789.1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47848

AN:

151602

Hom.:

9976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.0126

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.285

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

GnomAD4 genome

AF:

0.316

AC:

47932

AN:

151722

Hom.:

10002

Cov.:

AF XY:

0.311

AC XY:

23030

AN XY:

74120

show subpopulations

African (AFR)

AF:

0.594

AC:

24542

AN:

41344

American (AMR)

AF:

0.207

AC:

3156

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1163

AN:

3464

East Asian (EAS)

AF:

0.0126

AC:

AN:

5148

South Asian (SAS)

AF:

0.154

AC:

741

AN:

4816

European-Finnish (FIN)

AF:

0.206

AC:

2162

AN:

10482

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15255

AN:

67922

Other (OTH)

AF:

0.291

AC:

612

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

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:

0.254

Hom.:

17208

Bravo

AF:

0.327

Asia WGS

AF:

0.140

AC:

488

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.6

(source)

DANN

Benign

0.47

PhyloP100

-0.59

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over