12-112987289-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002535.3(OAS2):c.429G>A(p.Leu143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,206 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: OAS2 NM_002535.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00700

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-112987289-G-A is Benign according to our data. Variant chr12-112987289-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.007 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAS2	NM_002535.3	c.429G>A	p.Leu143=	synonymous_variant	2/10	ENST00000392583.7
OAS2	NM_016817.3	c.429G>A	p.Leu143=	synonymous_variant	2/11
OAS2	NM_001032731.2	c.429G>A	p.Leu143=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAS2	ENST00000392583.7	c.429G>A	p.Leu143=	synonymous_variant	2/10	1	NM_002535.3	P2
	ENST00000552784.1	n.353+30110C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000835 AC: 209 AN: 250426 Hom.: 0 AF XY: 0.000826 AC XY: 112 AN XY: 135654

Gnomad AFR exome AF: 0.000442

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00124 AC: 1811 AN: 1461884 Hom.: 4 Cov.: 36 AF XY: 0.00118 AC XY: 855 AN XY: 727242

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000738

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00150

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.000821 AC: 125 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000792 AC XY: 59 AN XY: 74486

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000324 Hom.: 0

Bravo AF: 0.000816

EpiCase AF: 0.00136

EpiControl AF: 0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.63
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs111979570; hg19: chr12-113425094;