Genetic Variant OAS2:c.1179+14T>C (chr12-113003116-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002535.3(OAS2):c.1179+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,611,860 control chromosomes in the GnomAD database, including 135,390 homozygotes. 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: 𝑓 0.34 ( 10490 hom., cov: 32)

Exomes 𝑓: 0.41 ( 124900 hom. )

Consequence

OAS2
NM_002535.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.480

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:

ENSG00000257452 (HGNC:):

ENSG00000257452 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAS2	NM_002535.3 link	c.1179+14T>C		intron_variant	Intron 6 of 9	ENST00000392583.7	NP_002526.2	P29728-2
OAS2	NM_016817.3 link	c.1179+14T>C		intron_variant	Intron 6 of 10		NP_058197.2	P29728-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAS2	ENST00000392583.7 link	c.1179+14T>C		intron_variant	Intron 6 of 9	1	NM_002535.3	ENSP00000376362.3		P29728-2

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51956

AN:

151984

Hom.:

10487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.422

AC:

105604

AN:

250486

Hom.:

23671

AF XY:

0.421

AC XY:

56908

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.432

Gnomad SAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.408

AC:

596217

AN:

1459758

Hom.:

124900

Cov.:

AF XY:

0.408

AC XY:

296537

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.520

Gnomad4 ASJ exome

AF:

0.389

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.516

Gnomad4 NFE exome

AF:

0.408

Gnomad4 OTH exome

AF:

0.388

GnomAD4 genome

AF:

0.342

AC:

51964

AN:

152102

Hom.:

10490

Cov.:

AF XY:

0.351

AC XY:

26073

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.414

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.399

Hom.:

18026

Bravo

AF:

0.328

Asia WGS

AF:

0.374

AC:

1299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over