rs141277168

Variant names:

• chr12-112997557-C-T
• rs141277168
• NM_002535.3:c.665C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-112997557-C-T
• chr12-112997557-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002535.3(OAS2):​c.665C>T​(p.Pro222Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: OAS2 NM_002535.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.14
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043819755).

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.665C>T	p.Pro222Leu	missense	Exon 4 of 10	NP_002526.2	P29728-2
	OAS2	NM_016817.3		c.665C>T	p.Pro222Leu	missense	Exon 4 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.665C>T	p.Pro222Leu	missense	Exon 4 of 10	ENSP00000376362.3	P29728-2
	OAS2	ENST00000342315.8	TSL:1	c.665C>T	p.Pro222Leu	missense	Exon 4 of 11	ENSP00000342278.4	P29728-1
	OAS2	ENST00000620097.2	TSL:5	c.557C>T	p.Pro186Leu	missense	Exon 5 of 11	ENSP00000483679.2	A0A087X0V5

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

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: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000358 AC: 90 AN: 251114 AF XY: 0.000361

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000731

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000338 AC: 494 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.000333 AC XY: 242 AN XY: 727198

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86230

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000419 AC: 466 AN: 1111950

Other (OTH) AF: 0.000215 AC: 13 AN: 60388

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74318

African (AFR) AF: 0.000193 AC: 8 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000570 Hom.: 0

Bravo AF: 0.000374

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000478 AC: 58

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000653

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	0.089
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.10
DANN	Benign	0.61
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.32	N
PhyloP100		-2.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.0060
Sift	Benign	0.38	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.049
MVP		0.29
MPC		0.17
ClinPred		0.015	T
GERP RS		-7.6
Varity_R		0.015
gMVP		0.27
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs141277168; hg19: chr12-113435362; COSMIC: COSV60801049; COSMIC: COSV60801049;