12-113010483-A-G

Variant names:

• chr12-113010483-A-G
• rs15895
• ENST00000342315.8:c.2159A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4 BA1

The NM_016817.3(OAS2):​c.2159A>G​(p.Ter720Trpext*?) 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 NM_016817.3 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 59 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: Likely_benign. The variant received -6 ACMG points.

• PM4: Stoplost variant in NM_016817.3 Downstream stopcodon found after 749 codons.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	NM_002535.3	MANE Select	c.*1228A>G		3_prime_UTR	Exon 10 of 10	NP_002526.2	P29728-2
	OAS2	NM_016817.3		c.2159A>G	p.Ter720Trpext*?	stop_lost	Exon 11 of 11	NP_058197.2	P29728-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000342315.8	TSL:1	c.2159A>G	p.Ter720Trpext*?	stop_lost	Exon 11 of 11	ENSP00000342278.4	P29728-1
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.*1228A>G		3_prime_UTR	Exon 10 of 10	ENSP00000376362.3	P29728-2
	OAS2	ENST00000680122.1		c.*2503A>G		3_prime_UTR	Exon 9 of 9	ENSP00000505194.1	A0A7P0T8H9

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

GnomAD2 exomes AF: 0.751 AC: 187410 AN: 249656 AF XY: 0.742

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 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

African (AFR) AF: 0.948 AC: 31681 AN: 33410

American (AMR) AF: 0.820 AC: 36520 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14438 AN: 26090

East Asian (EAS) AF: 0.989 AC: 39237 AN: 39682

South Asian (SAS) AF: 0.803 AC: 69104 AN: 86016

European-Finnish (FIN) AF: 0.779 AC: 41074 AN: 52750

Middle Eastern (MID) AF: 0.630 AC: 3630 AN: 5760

European-Non Finnish (NFE) AF: 0.647 AC: 718731 AN: 1111396

Other (OTH) AF: 0.694 AC: 41886 AN: 60332

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

African (AFR) AF: 0.938 AC: 38967 AN: 41544

American (AMR) AF: 0.765 AC: 11693 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1894 AN: 3464

East Asian (EAS) AF: 0.994 AC: 5141 AN: 5170

South Asian (SAS) AF: 0.818 AC: 3944 AN: 4820

European-Finnish (FIN) AF: 0.774 AC: 8187 AN: 10584

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44713 AN: 67962

Other (OTH) AF: 0.724 AC: 1530 AN: 2112

Alfa AF: 0.687 Hom.: 121062

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 v4.9

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
PhyloP100		0.032
GERP RS		0.85
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: rs15895; hg19: chr12-113448288; COSMIC: COSV107424777;