12-112987349-C-G

Variant names:

• chr12-112987349-C-G
• rs1293767
• ENST00000449768.2:c.489C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032731.2(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 NM_001032731.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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]

ENSG00000257452 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.448+41C>G		intron_variant	Intron 2 of 9	ENST00000392583.7	NP_002526.2
OAS2	NM_001032731.2	c.489C>G	p.Ser163Arg	missense_variant	Exon 2 of 2		NP_001027903.1
OAS2	NM_016817.3	c.448+41C>G		intron_variant	Intron 2 of 10		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.448+41C>G		intron_variant	Intron 2 of 9	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119187 AN: 151998 Hom.: 47779 Cov.: 31

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

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.: 60 AF XY: 0.708 AC XY: 513409 AN XY: 725266

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.: 31 AF XY: 0.790 AC XY: 58754 AN XY: 74372

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	T
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	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.019
Sift	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Vest4		0.069
MutPred		0.35		Gain of catalytic residue at S163 (P = 0.0014);
ClinPred		0.0024	T
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

Other links and lift over

dbSNP: rs1293767; hg19: chr12-113425154;