Variant chr12-112987349-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000449768.2(OAS2):c.489C>G(p.Ser163Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,610,684 control chromosomes in the GnomAD database, including 415,845 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 47840 hom., cov: 31)

Exomes 𝑓: 0.71 ( 368005 hom. )

Consequence

OAS2
ENST00000449768.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Variant links:

Genes affected

OAS2 (HGNC:8087): (2'-5'-oligoadenylate synthetase 2) This gene encodes a member of the 2-5A synthetase family, essential proteins involved in the innate immune response to viral infection. The encoded protein is induced by interferons and uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates (2-5As). These molecules activate latent RNase L, which results in viral RNA degradation and the inhibition of viral replication. The three known members of this gene family are located in a cluster on chromosome 12. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OAS2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0340443E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OAS2	NM_002535.3 linkuse as main transcript	c.448+41C>G		intron_variant		ENST00000392583.7
OAS2	NM_001032731.2 linkuse as main transcript	c.489C>G	p.Ser163Arg	missense_variant	2/2
OAS2	NM_016817.3 linkuse as main transcript	c.448+41C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS2	ENST00000392583.7 linkuse as main transcript	c.448+41C>G		intron_variant		1	NM_002535.3	P2	P29728-2
	ENST00000552784.1 linkuse as main transcript	n.353+30050G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119187

AN:

151998

Hom.:

47779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.945

Gnomad AMI

AF:

0.639

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.809

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.735

GnomAD3 exomes

AF:

0.764

AC:

187790

AN:

245930

Hom.:

72912

AF XY:

0.756

AC XY:

101041

AN XY:

133566

show subpopulations

Gnomad AFR exome

AF:

0.951

Gnomad AMR exome

AF:

0.835

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.922

Gnomad SAS exome

AF:

0.795

Gnomad FIN exome

AF:

0.802

Gnomad NFE exome

AF:

0.692

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.707

AC:

1030561

AN:

1458568

Hom.:

368005

Cov.:

AF XY:

0.708

AC XY:

513409

AN XY:

725266

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.906

Gnomad4 SAS exome

AF:

0.796

Gnomad4 FIN exome

AF:

0.795

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.784

AC:

119310

AN:

152116

Hom.:

47840

Cov.:

AF XY:

0.790

AC XY:

58754

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.945

Gnomad4 AMR

AF:

0.786

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.790

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.738

Alfa

AF:

0.685

Hom.:

19820

Bravo

AF:

0.791

TwinsUK

AF:

0.680

AC:

2521

ALSPAC

AF:

0.690

AC:

2660

ESP6500AA

AF:

0.942

AC:

4087

ESP6500EA

AF:

0.683

AC:

5853

ExAC

AF:

0.764

AC:

92550

Asia WGS

AF:

0.875

AC:

3043

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.7

DANN

Benign

0.44

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

-0.68

REVEL

Benign

0.019

Sift

Benign

0.43

Sift4G

Pathogenic

0.0

Vest4

0.069

MutPred

0.35

Gain of catalytic residue at S163 (P = 0.0014);

ClinPred

0.0024

GERP RS

0.025

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