rs2758331

Variant names:

• chr6-159684038-C-A
• rs2758331
• NM_000636.4:c.523+816G>T

Variant summary

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

The NM_000636.4(SOD2):​c.523+816G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,950 control chromosomes in the GnomAD database, including 13,616 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 (13616 hom., cov: 32)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 45 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=-0.73).
• 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 rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.523+816G>T		intron_variant	Intron 4 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.523+816G>T		intron_variant	Intron 4 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61163 AN: 151832 Hom.: 13606 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61171 AN: 151950 Hom.: 13616 Cov.: 32 AF XY: 0.400 AC XY: 29726 AN XY: 74256

African (AFR) AF: 0.223 AC: 9231 AN: 41418

American (AMR) AF: 0.487 AC: 7437 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3468

East Asian (EAS) AF: 0.132 AC: 685 AN: 5170

South Asian (SAS) AF: 0.475 AC: 2290 AN: 4816

European-Finnish (FIN) AF: 0.463 AC: 4872 AN: 10532

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33563 AN: 67964

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.471 Hom.: 35578

Bravo AF: 0.394

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		1.1
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: rs2758331; hg19: chr6-160105070; COSMIC: COSV61622888; COSMIC: COSV61622888;