Variant chr12-112995310-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000392583.7(OAS2):c.463C>A(p.Pro155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OAS2
ENST00000392583.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37892687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAS2	NM_002535.3 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	3/10	ENST00000392583.7	NP_002526.2
OAS2	NM_016817.3 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	3/11		NP_058197.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	3/10	1	NM_002535.3	ENSP00000376362	P2	P29728-2
	ENST00000552784.1 linkuse as main transcript	n.353+22089G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245048

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455858

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723872

show subpopulations

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.463C>A (p.P155T) alteration is located in exon 3 (coding exon 3) of the OAS2 gene. This alteration results from a C to A substitution at nucleotide position 463, causing the proline (P) at amino acid position 155 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.;T

Eigen

Benign

0.069

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

M;M;.;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

D;D;D;.

REVEL

Benign

0.11

Sift

Uncertain

0.0040

D;D;D;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.99

D;D;.;.

Vest4

0.34

MutPred

0.64

Gain of catalytic residue at W158 (P = 0.0038);Gain of catalytic residue at W158 (P = 0.0038);.;Gain of catalytic residue at W158 (P = 0.0038);

MVP

0.36

MPC

0.73

ClinPred

0.85

GERP RS

3.1

Varity_R

0.25

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over