12-113003116-T-C

Variant names:

• chr12-113003116-T-C
• rs2072137
• NM_002535.3:c.1179+14T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 24 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 -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.

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.1179+14T>C		intron	N/A	NP_002526.2
	OAS2	NM_016817.3		c.1179+14T>C		intron	N/A	NP_058197.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAS2	ENST00000392583.7	TSL:1 MANE Select	c.1179+14T>C		intron	N/A	ENSP00000376362.3
	OAS2	ENST00000342315.8	TSL:1	c.1179+14T>C		intron	N/A	ENSP00000342278.4
	OAS2	ENST00000620097.2	TSL:5	c.1071+14T>C		intron	N/A	ENSP00000483679.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51956 AN: 151984 Hom.: 10487 Cov.: 32

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

GnomAD2 exomes AF: 0.422 AC: 105604 AN: 250486 AF XY: 0.421

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 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.: 33 AF XY: 0.408 AC XY: 296537 AN XY: 726262

African (AFR) AF: 0.101 AC: 3364 AN: 33438

American (AMR) AF: 0.520 AC: 23216 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10145 AN: 26104

East Asian (EAS) AF: 0.461 AC: 18292 AN: 39670

South Asian (SAS) AF: 0.408 AC: 35142 AN: 86132

European-Finnish (FIN) AF: 0.516 AC: 27551 AN: 53388

Middle Eastern (MID) AF: 0.352 AC: 2028 AN: 5764

European-Non Finnish (NFE) AF: 0.408 AC: 453075 AN: 1110308

Other (OTH) AF: 0.388 AC: 23404 AN: 60296

GnomAD4 genome AF: 0.342 AC: 51964 AN: 152102 Hom.: 10490 Cov.: 32 AF XY: 0.351 AC XY: 26073 AN XY: 74344

African (AFR) AF: 0.115 AC: 4781 AN: 41512

American (AMR) AF: 0.445 AC: 6793 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2137 AN: 5174

South Asian (SAS) AF: 0.409 AC: 1972 AN: 4820

European-Finnish (FIN) AF: 0.515 AC: 5446 AN: 10566

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28156 AN: 67962

Other (OTH) AF: 0.337 AC: 711 AN: 2110

Alfa AF: 0.391 Hom.: 23927

Bravo AF: 0.328

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072137; hg19: chr12-113440921; COSMIC: COSV60802328; COSMIC: COSV60802328;