chr12-112987088-C-G

Variant names:

• chr12-112987088-C-G
• rs2072138
• NM_002535.3:c.228C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002535.3(OAS2):​c.228C>G​(p.Thr76Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,842 control chromosomes in the GnomAD database, including 62,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5479 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57180 hom.)
• Consequence: OAS2 NM_002535.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.609 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	NM_002535.3	MANE Select	c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 10	NP_002526.2
	OAS2	NM_016817.3		c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 11	NP_058197.2
	OAS2	NM_001032731.2		c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 2	NP_001027903.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 10	ENSP00000376362.3
	OAS2	ENST00000342315.8	TSL:1	c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 11	ENSP00000342278.4
	OAS2	ENST00000449768.2	TSL:1	c.228C>G	p.Thr76Thr	synonymous	Exon 2 of 2	ENSP00000411763.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39944 AN: 151908 Hom.: 5481 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.263 AC: 66092 AN: 251338 AF XY: 0.260

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.326

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0882

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.276 AC: 404040 AN: 1461816 Hom.: 57180 Cov.: 37 AF XY: 0.274 AC XY: 199146 AN XY: 727196

African (AFR) AF: 0.225 AC: 7549 AN: 33478

American (AMR) AF: 0.329 AC: 14698 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6042 AN: 26136

East Asian (EAS) AF: 0.113 AC: 4503 AN: 39700

South Asian (SAS) AF: 0.221 AC: 19054 AN: 86258

European-Finnish (FIN) AF: 0.266 AC: 14192 AN: 53420

Middle Eastern (MID) AF: 0.257 AC: 1481 AN: 5768

European-Non Finnish (NFE) AF: 0.289 AC: 320856 AN: 1111938

Other (OTH) AF: 0.259 AC: 15665 AN: 60396

GnomAD4 genome AF: 0.263 AC: 39956 AN: 152026 Hom.: 5479 Cov.: 32 AF XY: 0.261 AC XY: 19386 AN XY: 74312

African (AFR) AF: 0.233 AC: 9657 AN: 41448

American (AMR) AF: 0.322 AC: 4917 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3470

East Asian (EAS) AF: 0.0863 AC: 446 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4810

European-Finnish (FIN) AF: 0.268 AC: 2829 AN: 10566

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19247 AN: 67960

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.235 Hom.: 1427

Bravo AF: 0.269

Asia WGS AF: 0.176 AC: 618 AN: 3478

EpiCase AF: 0.287

EpiControl AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2072138; hg19: chr12-113424893; COSMIC: COSV60802381;