12-112995314-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 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. 12/21 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

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18529457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS2	NM_002535.3	c.467G>T	p.Ser156Ile	missense_variant	3/10	ENST00000392583.7
OAS2	NM_016817.3	c.467G>T	p.Ser156Ile	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS2	ENST00000392583.7	c.467G>T	p.Ser156Ile	missense_variant	3/10	1	NM_002535.3	P2
	ENST00000552784.1	n.353+22085C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000325 AC: 8 AN: 245868 Hom.: 0 AF XY: 0.0000527 AC XY: 7 AN XY: 132734

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 SAS exome AF: 0.000276

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000212

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.467G>T (p.S156I) alteration is located in exon 3 (coding exon 3) of the OAS2 gene. This alteration results from a G to T substitution at nucleotide position 467, causing the serine (S) at amino acid position 156 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M;M;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N;N;D;.
REVEL	Benign	0.093
Sift	Uncertain	0.010	D;D;D;.
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.17
MutPred		0.55		Gain of catalytic residue at W158 (P = 0.0057);Gain of catalytic residue at W158 (P = 0.0057);.;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

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: rs1555228618; hg19: chr12-113433119;