6-159692840-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000636.4(SOD2):c.47T>C(p.Val16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,610,644 control chromosomes in the GnomAD database, including 197,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,risk factor (no stars).

Frequency

Genomes: 𝑓 0.47 ( 17262 hom., cov: 32)

Exomes 𝑓: 0.49 ( 180259 hom. )

Consequence

SOD2
NM_000636.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity; risk factor no assertion criteria provided P:1B:1O:1

Conservation

PhyloP100: 2.20

Publications

1111 publications found

Variant links:

Genes affected

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 Gene-Disease associations (from GenCC):

cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SOD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.9671322E-5).

BP6

Variant 6-159692840-A-G is Benign according to our data. Variant chr6-159692840-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity|risk_factor. ClinVar VariationId is 14751.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.47T>C	p.Val16Ala	missense_variant	Exon 2 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.47T>C	p.Val16Ala	missense_variant	Exon 2 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71427

AN:

151824

Hom.:

17245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.474

GnomAD2 exomes

AF:

0.484

AC:

117709

AN:

243226

AF XY:

0.484

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.513

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.492

AC:

717843

AN:

1458702

Hom.:

180259

Cov.:

AF XY:

0.491

AC XY:

356365

AN XY:

725526

show subpopulations

African (AFR)

AF:

0.429

AC:

14335

AN:

33448

American (AMR)

AF:

0.613

AC:

27151

AN:

44282

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

13196

AN:

26080

East Asian (EAS)

AF:

0.131

AC:

5180

AN:

39586

South Asian (SAS)

AF:

0.519

AC:

44664

AN:

86044

European-Finnish (FIN)

AF:

0.481

AC:

25221

AN:

52464

Middle Eastern (MID)

AF:

0.442

AC:

2532

AN:

5730

European-Non Finnish (NFE)

AF:

0.501

AC:

556856

AN:

1110792

Other (OTH)

AF:

0.476

AC:

28708

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19130

38260

57389

76519

95649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16152

32304

48456

64608

80760

<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:

0.470

AC:

71475

AN:

151942

Hom.:

17262

Cov.:

AF XY:

0.466

AC XY:

34579

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.425

AC:

17591

AN:

41436

American (AMR)

AF:

0.537

AC:

8200

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1800

AN:

3466

East Asian (EAS)

AF:

0.144

AC:

742

AN:

5170

South Asian (SAS)

AF:

0.512

AC:

2468

AN:

4822

European-Finnish (FIN)

AF:

0.467

AC:

4921

AN:

10542

Middle Eastern (MID)

AF:

0.466

AC:

136

AN:

292

European-Non Finnish (NFE)

AF:

0.503

AC:

34180

AN:

67916

Other (OTH)

AF:

0.469

AC:

992

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1957

3914

5870

7827

9784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.486

Hom.:

66682

Bravo

AF:

0.472

TwinsUK

AF:

0.490

AC:

1818

ALSPAC

AF:

0.477

AC:

1839

ESP6500AA

AF:

0.420

AC:

1849

ESP6500EA

AF:

0.500

AC:

4303

ExAC

AF:

0.476

AC:

57687

Asia WGS

AF:

0.349

AC:

1214

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity; risk factor

Submissions summary: Pathogenic:1Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Microvascular complications of diabetes, susceptibility to, 6

Pathogenic:1Other:1

Jan 01, 2007

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

Jan 01, 2007

iDNA Genomics

Significance:Likely risk allele

Review Status:no assertion criteria provided

Collection Method:reference population

SOD2 POLYMORPHISM

Benign:1

Jan 01, 2007

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.2

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0

.;.;.;.;.;T;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.0

.;T;.;T;T;T;T;T

MetaRNN

Benign

0.000040

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;.;.;.;.;.;.;.

PhyloP100

2.2

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.35

N;N;N;N;N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.93

T;T;T;T;T;T;T;T

Sift4G

Benign

0.98

T;T;T;T;T;.;.;T

Vest4

0.034

ClinPred

0.0093

GERP RS

3.1

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.24

Mutation Taster

=296/4

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