12-113006312-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.1469-101C>G		intron_variant	Intron 7 of 9	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.1469-101C>G		intron_variant	Intron 7 of 10		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.1469-101C>G		intron_variant	Intron 7 of 9	1	NM_002535.3	ENSP00000376362.3

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

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.484

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

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.501

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.37

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: rs2240185; hg19: chr12-113444117;