12-113010483-A-G

Variant summary

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

The ENST00000342315.8(OAS2):c.2159A>G(p.Ter720TrpextTer8) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,612,108 control chromosomes in the GnomAD database, including 391,934 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 (46180 hom., cov: 31)
  • Exomes 𝑓: 0.68 (345754 hom.)
• Consequence: OAS2 ENST00000342315.8 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.816505).
• 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	UniProt
OAS2	NM_002535.3	c.*1228A>G		3_prime_UTR_variant	10/10	ENST00000392583.7
OAS2	NM_016817.3	c.2159A>G	p.Ter720TrpextTer8	stop_lost	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS2	ENST00000392583.7	c.*1228A>G		3_prime_UTR_variant	10/10	1	NM_002535.3	P2
	ENST00000552784.1	n.353+6916T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116656 AN: 152028 Hom.: 46114 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.722

GnomAD3 exomes AF: 0.751 AC: 187410 AN: 249656 Hom.: 72231 AF XY: 0.742 AC XY: 100121 AN XY: 134970

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.806

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.695

GnomAD4 exome AF: 0.682 AC: 996301 AN: 1459962 Hom.: 345754 Cov.: 40 AF XY: 0.684 AC XY: 496706 AN XY: 726268

Gnomad4 AFR exome AF: 0.948

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.779

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.768 AC: 116786 AN: 152146 Hom.: 46180 Cov.: 31 AF XY: 0.774 AC XY: 57587 AN XY: 74382

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.724

Alfa AF: 0.668 Hom.: 80676

Bravo AF: 0.775

TwinsUK AF: 0.635 AC: 2356

ALSPAC AF: 0.648 AC: 2497

ESP6500AA AF: 0.933 AC: 4112

ESP6500EA AF: 0.656 AC: 5639

ExAC AF: 0.753 AC: 91467

Asia WGS AF: 0.901 AC: 3131 AN: 3478

EpiCase AF: 0.637

EpiControl AF: 0.636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.5
Dann	Benign	0.72
Eigen	Benign	0.11
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.093	N
MutationTaster	Benign	1.0	P;P
GERP RS		0.85

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: rs15895; hg19: chr12-113448288;