12-113011311-G-C

Position:

• chr12-113011311-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002535.3(OAS2):​c.*2056G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,170 control chromosomes in the GnomAD database, including 46,084 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 0.77 (46083 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: OAS2 NM_002535.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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]

OAS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS2	NM_002535.3	c.*2056G>C		3_prime_UTR_variant	10/10	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.*827G>C		3_prime_UTR_variant	11/11		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.*2056G>C		3_prime_UTR_variant	10/10	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116526 AN: 152048 Hom.: 46017 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.767 AC: 116656 AN: 152166 Hom.: 46083 Cov.: 32 AF XY: 0.774 AC XY: 57532 AN XY: 74376

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.722

Alfa AF: 0.727 Hom.: 5107

Bravo AF: 0.773

Asia WGS AF: 0.900 AC: 3129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.47

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: rs1058480; hg19: chr12-113449116;