12-112978758-G-A

Variant names:

• chr12-112978758-G-A
• rs56249095
• NM_002535.3:c.150G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002535.3(OAS2):​c.150G>A​(p.Gln50Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,613,890 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (10 hom.)
• Consequence: OAS2 NM_002535.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.819
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-112978758-G-A is Benign according to our data. Variant chr12-112978758-G-A is described in ClinVar as Benign. ClinVar VariationId is 722500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.819 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00101 (154/152302) while in subpopulation EAS AF = 0.0269 (139/5176). AF 95% confidence interval is 0.0232. There are 2 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002535.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	NM_002535.3	MANE Select	c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 10	NP_002526.2	P29728-2
	OAS2	NM_016817.3		c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 11	NP_058197.2	P29728-1
	OAS2	NM_001032731.2		c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 2	NP_001027903.1	P29728-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 10	ENSP00000376362.3	P29728-2
	OAS2	ENST00000342315.8	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 11	ENSP00000342278.4	P29728-1
	OAS2	ENST00000449768.2	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 1 of 2	ENSP00000411763.2	P29728-3

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00194 AC: 487 AN: 250446 AF XY: 0.00186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0251

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000690 AC: 1009 AN: 1461588 Hom.: 10 Cov.: 30 AF XY: 0.000681 AC XY: 495 AN XY: 727086

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000336 AC: 15 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0228 AC: 905 AN: 39676

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86210

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111866

Other (OTH) AF: 0.000696 AC: 42 AN: 60388

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0269 AC: 139 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000190 Hom.: 0

Bravo AF: 0.00147

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.82
PromoterAI		0.016	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56249095; hg19: chr12-113416563; COSMIC: COSV107424802;