rs2855116

Positions:

• chr6-159685093-A-C

Variant summary

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

The NM_000636.4(SOD2):​c.344-60T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,299,976 control chromosomes in the GnomAD database, including 140,976 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 0.40 (13604 hom., cov: 31)
  • Exomes 𝑓: 0.47 (127372 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.344-60T>G		intron_variant		ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.344-60T>G		intron_variant		1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61123 AN: 151784 Hom.: 13594 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.465 AC: 534396 AN: 1148074 Hom.: 127372 AF XY: 0.466 AC XY: 265674 AN XY: 570166

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.402 AC: 61131 AN: 151902 Hom.: 13604 Cov.: 31 AF XY: 0.400 AC XY: 29705 AN XY: 74238

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.414

Alfa AF: 0.474 Hom.: 21588

Bravo AF: 0.394

Asia WGS AF: 0.315 AC: 1096 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	9.2
DANN	Benign	0.70

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: rs2855116; hg19: chr6-160106125; COSMIC: COSV61623438;