12-112984508-T-A

Variant names:

• chr12-112984508-T-A
• rs11513733
• NM_002535.3:c.178-2530T>A

Variant summary

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

The NM_002535.3(OAS2):​c.178-2530T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,266 control chromosomes in the GnomAD database, including 667 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 0.080 (667 hom., cov: 33)
• Consequence: OAS2 NM_002535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.178-2530T>A		intron_variant	Intron 1 of 9	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.178-2530T>A		intron_variant	Intron 1 of 10		NP_058197.2
OAS2	NM_001032731.2	c.178-2530T>A		intron_variant	Intron 1 of 1		NP_001027903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.178-2530T>A		intron_variant	Intron 1 of 9	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12197 AN: 152148 Hom.: 668 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0801 AC: 12192 AN: 152266 Hom.: 667 Cov.: 33 AF XY: 0.0788 AC XY: 5862 AN XY: 74434

African (AFR) AF: 0.0204 AC: 849 AN: 41570

American (AMR) AF: 0.0508 AC: 778 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 324 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0502 AC: 242 AN: 4820

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8287 AN: 67998

Other (OTH) AF: 0.0720 AC: 152 AN: 2112

Alfa AF: 0.102 Hom.: 99

Bravo AF: 0.0706

Asia WGS AF: 0.0210 AC: 72 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		0.20
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: rs11513733; hg19: chr12-113422313;