12-113010483-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000342315.8(OAS2):​c.2159A>C​(p.Ter720Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: OAS2 ENST00000342315.8 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000342315.8 Downstream stopcodon found after 790 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342315.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	NM_002535.3	MANE Select	c.*1228A>C		3_prime_UTR	Exon 10 of 10	NP_002526.2
	OAS2	NM_016817.3		c.2159A>C	p.Ter720Serext*?	stop_lost	Exon 11 of 11	NP_058197.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000342315.8	TSL:1	c.2159A>C	p.Ter720Serext*?	stop_lost	Exon 11 of 11	ENSP00000342278.4
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.*1228A>C		3_prime_UTR	Exon 10 of 10	ENSP00000376362.3
	OAS2	ENST00000679877.1		n.*3981A>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000506110.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.73
Eigen	Benign	0.11
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.11	N
PhyloP100		0.032
GERP RS		0.85
Mutation Taster		=100/0	polymorphism

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;