Genetic Variant SOD2:c.93-471G>T (chr6-159693334-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000545162.5(SOD2):c.93-471G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 296,632 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SOD2
ENST00000545162.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0830

Publications

4 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.-167G>T		upstream_gene_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.-167G>T		upstream_gene_variant		1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

136842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000706

Gnomad ASJ

AF:

0.00242

Gnomad EAS

AF:

0.000219

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000248

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000127

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

AN:

159714

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

82706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3320

American (AMR)

AF:

0.000312

AC:

AN:

3204

Ashkenazi Jewish (ASJ)

AF:

0.00219

AC:

AN:

3660

East Asian (EAS)

AF:

0.00

AC:

AN:

9762

South Asian (SAS)

AF:

0.00

AC:

AN:

2968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

690

European-Non Finnish (NFE)

AF:

0.0000686

AC:

AN:

116560

Other (OTH)

AF:

0.000371

AC:

AN:

8092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000146

AC:

AN:

136918

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

AN XY:

66396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36652

American (AMR)

AF:

0.0000705

AC:

AN:

14184

Ashkenazi Jewish (ASJ)

AF:

0.00242

AC:

AN:

3306

East Asian (EAS)

AF:

0.000220

AC:

AN:

4546

South Asian (SAS)

AF:

0.00

AC:

AN:

4436

European-Finnish (FIN)

AF:

0.000248

AC:

AN:

8050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000127

AC:

AN:

62766

Other (OTH)

AF:

0.00

AC:

AN:

1898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.8

(source)

DANN

Benign

0.91

PhyloP100

-0.083

PromoterAI

-0.081

Neutral

(source)

Splicing

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