12-112987349-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S163S) has been classified as Uncertain significance.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032731.2. 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
	OAS2	NM_002535.3	MANE Select	c.448+41C>G		intron	N/A	NP_002526.2	P29728-2
	OAS2	NM_001032731.2		c.489C>G	p.Ser163Arg	missense	Exon 2 of 2	NP_001027903.1	P29728-3
	OAS2	NM_016817.3		c.448+41C>G		intron	N/A	NP_058197.2	P29728-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000449768.2	TSL:1	c.489C>G	p.Ser163Arg	missense	Exon 2 of 2	ENSP00000411763.2	P29728-3
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.448+41C>G		intron	N/A	ENSP00000376362.3	P29728-2
	OAS2	ENST00000342315.8	TSL:1	c.448+41C>G		intron	N/A	ENSP00000342278.4	P29728-1

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

GnomAD2 exomes AF: 0.764 AC: 187790 AN: 245930 AF XY: 0.756

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 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

African (AFR) AF: 0.953 AC: 31800 AN: 33380

American (AMR) AF: 0.828 AC: 36791 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 15309 AN: 26002

East Asian (EAS) AF: 0.906 AC: 35886 AN: 39616

South Asian (SAS) AF: 0.796 AC: 68391 AN: 85924

European-Finnish (FIN) AF: 0.795 AC: 42351 AN: 53296

Middle Eastern (MID) AF: 0.640 AC: 3671 AN: 5732

European-Non Finnish (NFE) AF: 0.679 AC: 753500 AN: 1109912

Other (OTH) AF: 0.711 AC: 42862 AN: 60270

GnomAD4 genome AF: 0.784 AC: 119310 AN: 152116 Hom.: 47840 Cov.: 31 AF XY: 0.790 AC XY: 58754 AN XY: 74372

African (AFR) AF: 0.945 AC: 39257 AN: 41520

American (AMR) AF: 0.786 AC: 12010 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2000 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4699 AN: 5158

South Asian (SAS) AF: 0.808 AC: 3892 AN: 4816

European-Finnish (FIN) AF: 0.790 AC: 8376 AN: 10596

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46752 AN: 67948

Other (OTH) AF: 0.738 AC: 1561 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
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
PhyloP100		0.19
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1293767; hg19: chr12-113425154; COSMIC: COSV107424776;