rs2758346

Variant names:

• chr6-159694389-C-T
• rs2758346
• ENST00000545162.5:c.93-1526G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000545162.5(SOD2):​c.93-1526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,776 control chromosomes in the GnomAD database, including 17,206 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 0.47 (17206 hom., cov: 31)
• Consequence: SOD2 ENST00000545162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-115-1526G>A		intron_variant	Intron 3 of 7		NP_001309746.1
SOD2	NM_001322819.2	c.-115-1526G>A		intron_variant	Intron 1 of 4		NP_001309748.1
SOD2	NM_001322820.2	c.-115-1526G>A		intron_variant	Intron 1 of 4		NP_001309749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.93-1526G>A		intron_variant	Intron 1 of 3	3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.93-1526G>A		intron_variant	Intron 1 of 3	3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-115-1526G>A		intron_variant	Intron 3 of 7	2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71292 AN: 151656 Hom.: 17190 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71336 AN: 151776 Hom.: 17206 Cov.: 31 AF XY: 0.465 AC XY: 34498 AN XY: 74138

African (AFR) AF: 0.426 AC: 17642 AN: 41372

American (AMR) AF: 0.533 AC: 8134 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1802 AN: 3470

East Asian (EAS) AF: 0.142 AC: 735 AN: 5168

South Asian (SAS) AF: 0.512 AC: 2466 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4903 AN: 10500

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34085 AN: 67894

Other (OTH) AF: 0.469 AC: 986 AN: 2104

Alfa AF: 0.496 Hom.: 15296

Bravo AF: 0.471

Asia WGS AF: 0.349 AC: 1213 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	0.13
DANN	Benign	0.83
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2758346; hg19: chr6-160115421;