rs2758339

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322816.2(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 NM_001322816.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SOD2	NM_000636.4	c.226+1109T>G		intron_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.226+1109T>G		intron_variant		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

Gnomad4 FIN exome AF: 1.00

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.439

Alfa AF: 0.433 Hom.: 2940

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

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

Publications

LitVar

Other links and lift over

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