rs2842958

Variant names:

• chr6-159687393-A-G
• rs2842958
• NM_000636.4:c.343+733T>C

Variant summary

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

The NM_000636.4(SOD2):​c.343+733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 151,904 control chromosomes in the GnomAD database, including 45,055 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 0.77 (45055 hom., cov: 30)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 11 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):

• microvascular complications of diabetes, susceptibility to, 6

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000636.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	NM_000636.4	MANE Select	c.343+733T>C		intron	N/A	NP_000627.2	P04179-1
	SOD2	NM_001024465.3		c.343+733T>C		intron	N/A	NP_001019636.1	P04179-1
	SOD2	NM_001024466.3		c.227-2360T>C		intron	N/A	NP_001019637.1	P04179-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.343+733T>C		intron	N/A	ENSP00000446252.1	P04179-1
	SOD2	ENST00000367055.8	TSL:1	c.343+733T>C		intron	N/A	ENSP00000356022.4	P04179-1
	SOD2	ENST00000881541.1		c.340+733T>C		intron	N/A	ENSP00000551600.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116324 AN: 151786 Hom.: 45028 Cov.: 30

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.766 AC: 116396 AN: 151904 Hom.: 45055 Cov.: 30 AF XY: 0.768 AC XY: 57000 AN XY: 74222

African (AFR) AF: 0.698 AC: 28865 AN: 41372

American (AMR) AF: 0.829 AC: 12674 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2630 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2761 AN: 5118

South Asian (SAS) AF: 0.853 AC: 4105 AN: 4812

European-Finnish (FIN) AF: 0.837 AC: 8832 AN: 10556

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54095 AN: 67982

Other (OTH) AF: 0.772 AC: 1631 AN: 2112

Alfa AF: 0.783 Hom.: 6078

Bravo AF: 0.759

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.97
DANN	Benign	0.26
PhyloP100		-1.0
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: rs2842958; hg19: chr6-160108425;