chr12-113010483-A-C

Position:

• chr12-113010483-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_016817.3(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 NM_016817.3 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]

OAS2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_016817.3 Downstream stopcodon found after 749 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS2	NM_002535.3	c.*1228A>C		3_prime_UTR_variant	10/10	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.2159A>C	p.Ter720Serext*?	stop_lost	11/11		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.*1228A>C		3_prime_UTR_variant	10/10	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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;