ENST00000449768.2:c.489C>A

Variant names:

• chr12-112987349-C-A
• rs1293767
• ENST00000449768.2:c.489C>A
• OAS2 p.Ser163Arg

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000449768.2(OAS2):​c.489C>A​(p.Ser163Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,610,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: OAS2 ENST00000449768.2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040543318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449768.2. 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>A		intron	N/A	NP_002526.2	P29728-2
	OAS2	NM_001032731.2		c.489C>A	p.Ser163Arg	missense	Exon 2 of 2	NP_001027903.1	P29728-3
	OAS2	NM_016817.3		c.448+41C>A		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>A	p.Ser163Arg	missense	Exon 2 of 2	ENSP00000411763.2	P29728-3
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.448+41C>A		intron	N/A	ENSP00000376362.3	P29728-2
	OAS2	ENST00000342315.8	TSL:1	c.448+41C>A		intron	N/A	ENSP00000342278.4	P29728-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152036 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 245930 AF XY: 0.0000374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000480 AC: 70 AN: 1458808 Hom.: 0 Cov.: 60 AF XY: 0.0000579 AC XY: 42 AN XY: 725382

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.0000675 AC: 3 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000568 AC: 63 AN: 1110086

Other (OTH) AF: 0.0000664 AC: 4 AN: 60278

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152036 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000121 Hom.: 19820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.26
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.19
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.018
Sift	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1293767;

hg19: chr12-113425154;