12-113006312-C-G

Variant names:

• chr12-113006312-C-G
• rs2240185
• NM_002535.3:c.1469-101C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002535.3(OAS2):​c.1469-101C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 979,668 control chromosomes in the GnomAD database, including 115,708 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 0.52 (20517 hom., cov: 32)
  • Exomes 𝑓: 0.48 (95191 hom.)
• Consequence: OAS2 NM_002535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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.1469-101C>G		intron	N/A	NP_002526.2
	OAS2	NM_016817.3		c.1469-101C>G		intron	N/A	NP_058197.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.1469-101C>G		intron	N/A	ENSP00000376362.3
	OAS2	ENST00000342315.8	TSL:1	c.1469-101C>G		intron	N/A	ENSP00000342278.4
	OAS2	ENST00000620097.2	TSL:5	c.1361-101C>G		intron	N/A	ENSP00000483679.2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78399 AN: 151910 Hom.: 20489 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.477 AC: 394971 AN: 827640 Hom.: 95191 AF XY: 0.479 AC XY: 196257 AN XY: 409958

African (AFR) AF: 0.595 AC: 11847 AN: 19906

American (AMR) AF: 0.551 AC: 10629 AN: 19302

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 7126 AN: 14800

East Asian (EAS) AF: 0.465 AC: 15210 AN: 32686

South Asian (SAS) AF: 0.539 AC: 21392 AN: 39706

European-Finnish (FIN) AF: 0.466 AC: 19001 AN: 40762

Middle Eastern (MID) AF: 0.506 AC: 1289 AN: 2546

European-Non Finnish (NFE) AF: 0.468 AC: 290546 AN: 620918

Other (OTH) AF: 0.484 AC: 17931 AN: 37014

GnomAD4 genome AF: 0.516 AC: 78475 AN: 152028 Hom.: 20517 Cov.: 32 AF XY: 0.517 AC XY: 38437 AN XY: 74302

African (AFR) AF: 0.593 AC: 24570 AN: 41468

American (AMR) AF: 0.550 AC: 8407 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1672 AN: 3464

East Asian (EAS) AF: 0.418 AC: 2162 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2593 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4831 AN: 10542

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32459 AN: 67970

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.498 Hom.: 2635

Bravo AF: 0.523

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.37
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs2240185; hg19: chr12-113444117;