12-112997634-G-T

Variant names:

• chr12-112997634-G-T
• rs144979086
• NM_002535.3:c.742G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002535.3(OAS2):​c.742G>T​(p.Val248Phe) variant causes a missense 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. 15/21 in silico tools predict 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: 33)
• Consequence: OAS2 NM_002535.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07874048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.742G>T	p.Val248Phe	missense_variant	Exon 4 of 10	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.742G>T	p.Val248Phe	missense_variant	Exon 4 of 11		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.742G>T	p.Val248Phe	missense_variant	Exon 4 of 10	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.0030
DANN	Benign	0.73
DEOGEN2	Benign	0.035	T;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.079	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N;N;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.65	N;N;N;.
REVEL	Benign	0.20
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.99	D;D;.;.
Vest4		0.15
MutPred		0.60		Gain of catalytic residue at A245 (P = 0.0507);Gain of catalytic residue at A245 (P = 0.0507);.;Gain of catalytic residue at A245 (P = 0.0507);
MVP		0.11
MPC		0.27
ClinPred		0.13	T
GERP RS		-7.4
Varity_R		0.086
gMVP		0.30

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: rs144979086; hg19: chr12-113435439;