rs2842960

Positions:

• chr6-159692289-C-T

Variant summary

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

The ENST00000452684.2(SOD2):​c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 724,018 control chromosomes in the GnomAD database, including 85,733 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 0.47 (17298 hom., cov: 31)
  • Exomes 𝑓: 0.48 (68435 hom.)
• Consequence: SOD2 ENST00000452684.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.226+372G>A		intron_variant		ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.226+372G>A		intron_variant		1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71530 AN: 151914 Hom.: 17282 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.480 AC: 274674 AN: 571984 Hom.: 68435 Cov.: 8 AF XY: 0.481 AC XY: 134842 AN XY: 280566

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.503

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.471 AC: 71575 AN: 152034 Hom.: 17298 Cov.: 31 AF XY: 0.466 AC XY: 34609 AN XY: 74312

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.473

Alfa AF: 0.502 Hom.: 5487

Bravo AF: 0.472

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2842960; hg19: chr6-160113321; COSMIC: COSV61623443; COSMIC: COSV61623443;