rs2758339

Variant names:

• chr6-159691552-A-C
• rs2758339
• ENST00000452684.2:c.*912T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-159691552-A-C
• chr6-159691552-A-T

Variant summary

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

The ENST00000452684.2(SOD2):​c.*912T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,972 control chromosomes in the GnomAD database, including 15,028 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 0.43 (15027 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: SOD2 ENST00000452684.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.226+1109T>G		intron_variant	Intron 2 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.226+1109T>G		intron_variant	Intron 2 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65880 AN: 151852 Hom.: 15015 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.434 AC: 65895 AN: 151970 Hom.: 15027 Cov.: 32 AF XY: 0.430 AC XY: 31959 AN XY: 74266

African (AFR) AF: 0.322 AC: 13337 AN: 41440

American (AMR) AF: 0.511 AC: 7800 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1781 AN: 3470

East Asian (EAS) AF: 0.142 AC: 737 AN: 5176

South Asian (SAS) AF: 0.481 AC: 2319 AN: 4820

European-Finnish (FIN) AF: 0.461 AC: 4858 AN: 10534

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33576 AN: 67950

Other (OTH) AF: 0.439 AC: 924 AN: 2106

Alfa AF: 0.457 Hom.: 6413

Bravo AF: 0.431

Asia WGS AF: 0.327 AC: 1136 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.55
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2758339; hg19: chr6-160112584; COSMIC: COSV61622913; COSMIC: COSV61622913;