12-112993031-T-G

Variant names:

• chr12-112993031-T-G
• rs1293762
• NM_002535.3:c.449-2265T>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.449-2265T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,992 control chromosomes in the GnomAD database, including 35,398 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 0.67 (35398 hom., cov: 32)
• Consequence: OAS2 NM_002535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.449-2265T>G		intron_variant	Intron 2 of 9	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.449-2265T>G		intron_variant	Intron 2 of 10		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.449-2265T>G		intron_variant	Intron 2 of 9	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101429 AN: 151874 Hom.: 35350 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.668 AC: 101536 AN: 151992 Hom.: 35398 Cov.: 32 AF XY: 0.674 AC XY: 50109 AN XY: 74306

African (AFR) AF: 0.843 AC: 34946 AN: 41462

American (AMR) AF: 0.685 AC: 10454 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4787 AN: 5178

South Asian (SAS) AF: 0.681 AC: 3275 AN: 4812

European-Finnish (FIN) AF: 0.660 AC: 6968 AN: 10552

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37689 AN: 67950

Other (OTH) AF: 0.614 AC: 1290 AN: 2102

Alfa AF: 0.636 Hom.: 9162

Bravo AF: 0.680

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		-0.42
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: rs1293762; hg19: chr12-113430836;