ENST00000452684.2:c.*858T>C

Variant names:

• chr6-159691606-A-G
• rs5746105
• ENST00000452684.2:c.*858T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000452684.2(SOD2):​c.*858T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,028 control chromosomes in the GnomAD database, including 6,251 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 0.29 (6251 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOD2 ENST00000452684.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.226+1055T>C		intron_variant	Intron 2 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.226+1055T>C		intron_variant	Intron 2 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43393 AN: 151910 Hom.: 6244 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.295

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.286 AC: 43423 AN: 152028 Hom.: 6251 Cov.: 32 AF XY: 0.292 AC XY: 21717 AN XY: 74300

African (AFR) AF: 0.235 AC: 9731 AN: 41460

American (AMR) AF: 0.292 AC: 4470 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2044 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1636 AN: 4826

European-Finnish (FIN) AF: 0.369 AC: 3887 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19859 AN: 67962

Other (OTH) AF: 0.293 AC: 618 AN: 2106

Alfa AF: 0.289 Hom.: 3615

Bravo AF: 0.277

Asia WGS AF: 0.334 AC: 1160 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	2.9
DANN	Benign	0.27
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5746105; hg19: chr6-160112638;