rs2297518

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000625.4(NOS2):c.1823C>T(p.Ser608Leu) variant causes a missense change. The variant allele was found at a frequency of 0.184 in 1,608,552 control chromosomes in the GnomAD database, including 28,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2373 hom., cov: 33)

Exomes 𝑓: 0.18 ( 26033 hom. )

Consequence

NOS2
NM_000625.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.41

Publications

244 publications found

Variant links:

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

NOS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028576553).

BP6

Variant 17-27769571-G-A is Benign according to our data. Variant chr17-27769571-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4 link	c.1823C>T	p.Ser608Leu	missense_variant	Exon 16 of 27	ENST00000313735.11	NP_000616.3	P35228-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11 link	c.1823C>T	p.Ser608Leu	missense_variant	Exon 16 of 27	1	NM_000625.4	ENSP00000327251.6		P35228-1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26142

AN:

151996

Hom.:

2375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.197

GnomAD2 exomes

AF:

0.177

AC:

44586

AN:

251380

AF XY:

0.183

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.185

AC:

269171

AN:

1456438

Hom.:

26033

Cov.:

AF XY:

0.186

AC XY:

134655

AN XY:

724896

show subpopulations

African (AFR)

AF:

0.118

AC:

3955

AN:

33392

American (AMR)

AF:

0.133

AC:

5966

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6589

AN:

26082

East Asian (EAS)

AF:

0.102

AC:

4056

AN:

39686

South Asian (SAS)

AF:

0.180

AC:

15467

AN:

86112

European-Finnish (FIN)

AF:

0.179

AC:

9559

AN:

53404

Middle Eastern (MID)

AF:

0.229

AC:

1316

AN:

5748

European-Non Finnish (NFE)

AF:

0.191

AC:

211002

AN:

1107092

Other (OTH)

AF:

0.187

AC:

11261

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

10099

20198

30297

40396

50495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7230

14460

21690

28920

36150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.172

AC:

26144

AN:

152114

Hom.:

2373

Cov.:

AF XY:

0.173

AC XY:

12838

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.121

AC:

5033

AN:

41494

American (AMR)

AF:

0.168

AC:

2565

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

890

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

774

AN:

5182

South Asian (SAS)

AF:

0.173

AC:

834

AN:

4814

European-Finnish (FIN)

AF:

0.188

AC:

1991

AN:

10578

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13156

AN:

67970

Other (OTH)

AF:

0.195

AC:

412

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1124

2248

3373

4497

5621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.188

Hom.:

13156

Bravo

AF:

0.170

TwinsUK

AF:

0.200

AC:

743

ALSPAC

AF:

0.189

AC:

727

ESP6500AA

AF:

0.113

AC:

500

ESP6500EA

AF:

0.195

AC:

1680

ExAC

AF:

0.178

AC:

21575

Asia WGS

AF:

0.140

AC:

486

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.197

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

NOS2-related disorder

Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

L;.;.

PhyloP100

6.4

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Benign

0.25

Sift

Benign

0.12

T;.;.

Sift4G

Benign

0.10

T;.;T

Polyphen

0.92

P;.;.

Vest4

0.24

MPC

2.6

ClinPred

0.023

GERP RS

5.3

Varity_R

0.46

gMVP

0.54

Mutation Taster

=88/12

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over