12-112995314-G-T

Variant names:

• chr12-112995314-G-T
• rs1555228618
• NM_002535.3:c.467G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002535.3(OAS2):​c.467G>T​(p.Ser156Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,456,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: OAS2 NM_002535.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172
• Publications: 0 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18529457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002535.3. 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.467G>T	p.Ser156Ile	missense	Exon 3 of 10	NP_002526.2	P29728-2
	OAS2	NM_016817.3		c.467G>T	p.Ser156Ile	missense	Exon 3 of 11	NP_058197.2	P29728-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.467G>T	p.Ser156Ile	missense	Exon 3 of 10	ENSP00000376362.3	P29728-2
	OAS2	ENST00000342315.8	TSL:1	c.467G>T	p.Ser156Ile	missense	Exon 3 of 11	ENSP00000342278.4	P29728-1
	OAS2	ENST00000620097.2	TSL:5	c.359G>T	p.Ser120Ile	missense	Exon 4 of 11	ENSP00000483679.2	A0A087X0V5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000325 AC: 8 AN: 245868 AF XY: 0.0000527

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1456586 Hom.: 0 Cov.: 30 AF XY: 0.0000235 AC XY: 17 AN XY: 724264

African (AFR) AF: 0.00 AC: 0 AN: 33090

American (AMR) AF: 0.00 AC: 0 AN: 43312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.000212 AC: 18 AN: 84808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110420

Other (OTH) AF: 0.0000332 AC: 2 AN: 60196

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.17
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.093
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.55		Gain of catalytic residue at W158 (P = 0.0057)
MVP		0.49
MPC		0.69
ClinPred		0.31	T
GERP RS		2.0
Varity_R		0.082
gMVP		0.40
Mutation Taster		=92/8	polymorphism

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: rs1555228618; hg19: chr12-113433119;