rs2758332

Positions:

• chr6-159685056-C-A
• chr6-159685056-C-T

Variant summary

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

The NM_000636.4(SOD2):​c.344-23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,554,900 control chromosomes in the GnomAD database, including 191,890 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 0.49 (18576 hom., cov: 30)
  • Exomes 𝑓: 0.49 (173314 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.344-23G>T		intron_variant		ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.344-23G>T		intron_variant		1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74131 AN: 151526 Hom.: 18558 Cov.: 30

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.486

GnomAD3 exomes AF: 0.479 AC: 100884 AN: 210598 Hom.: 25334 AF XY: 0.479 AC XY: 54997 AN XY: 114888

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.521

Gnomad FIN exome AF: 0.468

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.491 AC: 689231 AN: 1403256 Hom.: 173314 Cov.: 27 AF XY: 0.490 AC XY: 341611 AN XY: 696950

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.489 AC: 74179 AN: 151644 Hom.: 18576 Cov.: 30 AF XY: 0.483 AC XY: 35804 AN XY: 74108

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.482

Alfa AF: 0.502 Hom.: 3923

Bravo AF: 0.493

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.75

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: rs2758332; hg19: chr6-160106088; COSMIC: COSV61622892;