rs2758329

chr6-159677251-T-C

Variant summary

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

The NM_000636.4(SOD2):c.*5242A>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 0.453 in 151,976 control chromosomes in the GnomAD database, including 16,072 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 0.45 (16071 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.*5242A>G		3_prime_UTR_variant	5/5	ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.*5242A>G		3_prime_UTR_variant	5/5	1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68843 AN: 151852 Hom.: 16057 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.453 AC: 68865 AN: 151972 Hom.: 16071 Cov.: 31 AF XY: 0.448 AC XY: 33319 AN XY: 74300

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.450

Alfa AF: 0.491 Hom.: 4370

Bravo AF: 0.453

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs2758329; hg19: chr6-160098283;