chr12-112987214-C-A

Variant names:

• chr12-112987214-C-A
• NM_002535.3:c.354C>A

Variant summary

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

The NM_002535.3(OAS2):​c.354C>A​(p.Phe118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OAS2 NM_002535.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903

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=0.07634574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3	c.354C>A	p.Phe118Leu	missense_variant	Exon 2 of 10	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3	c.354C>A	p.Phe118Leu	missense_variant	Exon 2 of 11		NP_058197.2
OAS2	NM_001032731.2	c.354C>A	p.Phe118Leu	missense_variant	Exon 2 of 2		NP_001027903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7	c.354C>A	p.Phe118Leu	missense_variant	Exon 2 of 10	1	NM_002535.3	ENSP00000376362.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.85
DANN	Benign	0.65
DEOGEN2	Benign	0.038	T;.;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.29	T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.076	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.24	N;N;N;.
REVEL	Benign	0.022
Sift	Benign	0.12	T;T;T;.
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.0010	B;B;.;.
Vest4		0.051
MutPred		0.59		Gain of catalytic residue at W113 (P = 0.0118);Gain of catalytic residue at W113 (P = 0.0118);Gain of catalytic residue at W113 (P = 0.0118);Gain of catalytic residue at W113 (P = 0.0118);
MVP		0.10
MPC		0.19
ClinPred		0.043	T
GERP RS		-5.9
Varity_R		0.076
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-113425019;