Genetic Variant SOD2:c.344-60T>G (chr6-159685093-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000636.4(SOD2):c.344-60T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,299,976 control chromosomes in the GnomAD database, including 140,976 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 0.40 ( 13604 hom., cov: 31)

Exomes 𝑓: 0.47 ( 127372 hom. )

Consequence

SOD2
NM_000636.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

Publications

25 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.344-60T>G		intron_variant	Intron 3 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.344-60T>G		intron_variant	Intron 3 of 4	1	NM_000636.4	ENSP00000446252.1		P04179-1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61123

AN:

151784

Hom.:

13594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.418

GnomAD4 exome

AF:

0.465

AC:

534396

AN:

1148074

Hom.:

127372

AF XY:

0.466

AC XY:

265674

AN XY:

570166

show subpopulations

African (AFR)

AF:

0.216

AC:

5284

AN:

24484

American (AMR)

AF:

0.555

AC:

11643

AN:

20992

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

8809

AN:

19220

East Asian (EAS)

AF:

0.125

AC:

4218

AN:

33814

South Asian (SAS)

AF:

0.483

AC:

28002

AN:

57934

European-Finnish (FIN)

AF:

0.477

AC:

21967

AN:

46026

Middle Eastern (MID)

AF:

0.401

AC:

1974

AN:

4918

European-Non Finnish (NFE)

AF:

0.483

AC:

431394

AN:

892682

Other (OTH)

AF:

0.440

AC:

21105

AN:

48004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12484

24968

37452

49936

62420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12724

25448

38172

50896

63620

<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:

0.402

AC:

61131

AN:

151902

Hom.:

13604

Cov.:

AF XY:

0.400

AC XY:

29705

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.223

AC:

9234

AN:

41438

American (AMR)

AF:

0.487

AC:

7423

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1657

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

685

AN:

5182

South Asian (SAS)

AF:

0.476

AC:

2298

AN:

4826

European-Finnish (FIN)

AF:

0.463

AC:

4849

AN:

10480

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33547

AN:

67950

Other (OTH)

AF:

0.414

AC:

873

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1728

3456

5185

6913

8641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.455

Hom.:

38285

Bravo

AF:

0.394

Asia WGS

AF:

0.315

AC:

1096

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.2

(source)

DANN

Benign

0.70

PhyloP100

0.65

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over