Genetic Variant SOD2:c.*441G>A (chr6-159682052-C-T) – 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.*441G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 153,582 control chromosomes in the GnomAD database, including 6,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6051 hom., cov: 32)

Exomes 𝑓: 0.29 ( 67 hom. )

Consequence

SOD2
NM_000636.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

106 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):

microvascular complications of diabetes, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOD2	NM_000636.4	MANE Select	c.*441G>A	3_prime_UTR	Exon 5 of 5	NP_000627.2	P04179-1
SOD2	NM_001322814.2		c.*441G>A	3_prime_UTR	Exon 4 of 4	NP_001309743.1	P04179-2
SOD2	NM_001322819.2		c.*441G>A	3_prime_UTR	Exon 5 of 5	NP_001309748.1	P04179-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOD2	ENST00000538183.7	TSL:1 MANE Select	c.*441G>A	3_prime_UTR	Exon 5 of 5	ENSP00000446252.1	P04179-1
SOD2	ENST00000367055.8	TSL:1	c.*19+422G>A	intron	N/A	ENSP00000356022.4	P04179-1
SOD2	ENST00000942970.1		c.*441G>A	3_prime_UTR	Exon 5 of 5	ENSP00000613029.1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42194

AN:

151914

Hom.:

6049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.285

AC:

442

AN:

1550

Hom.:

Cov.:

AF XY:

0.308

AC XY:

269

AN XY:

872

show subpopulations

African (AFR)

AF:

0.188

AC:

AN:

American (AMR)

AF:

0.236

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.329

AC:

AN:

286

European-Finnish (FIN)

AF:

0.350

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.276

AC:

286

AN:

1038

Other (OTH)

AF:

0.297

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.278

AC:

42219

AN:

152032

Hom.:

6051

Cov.:

AF XY:

0.285

AC XY:

21207

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.198

AC:

8228

AN:

41476

American (AMR)

AF:

0.303

AC:

4637

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

952

AN:

3472

East Asian (EAS)

AF:

0.409

AC:

2116

AN:

5176

South Asian (SAS)

AF:

0.344

AC:

1655

AN:

4812

European-Finnish (FIN)

AF:

0.371

AC:

3903

AN:

10530

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.293

AC:

19895

AN:

67964

Other (OTH)

AF:

0.291

AC:

614

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1559

3117

4676

6234

7793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.283

Hom.:

17250

Bravo

AF:

0.268

Asia WGS

AF:

0.338

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.5

(source)

DANN

Benign

0.73

PhyloP100

0.031

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over