6-159701889-A-G

Variant names:

• chr6-159701889-A-G
• rs2758352
• ENST00000545162.5:c.93-9026T>C

Variant summary

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

The NM_001322817.2(SOD2):​c.-115-9026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,052 control chromosomes in the GnomAD database, including 44,675 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 0.76 (44675 hom., cov: 31)
• Consequence: SOD2 NM_001322817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 27 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322817.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	NM_001322817.2		c.-115-9026T>C		intron	N/A	NP_001309746.1
	SOD2	NM_001322819.2		c.-115-9026T>C		intron	N/A	NP_001309748.1
	SOD2	NM_001322820.2		c.-115-9026T>C		intron	N/A	NP_001309749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000545162.5	TSL:3	c.93-9026T>C		intron	N/A	ENSP00000441362.1
	SOD2	ENST00000535561.5	TSL:3	c.93-9026T>C		intron	N/A	ENSP00000445015.1
	SOD2	ENST00000546087.5	TSL:2	c.-115-9026T>C		intron	N/A	ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115958 AN: 151934 Hom.: 44649 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.763 AC: 116032 AN: 152052 Hom.: 44675 Cov.: 31 AF XY: 0.766 AC XY: 56910 AN XY: 74322

African (AFR) AF: 0.694 AC: 28744 AN: 41430

American (AMR) AF: 0.830 AC: 12685 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2592 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3017 AN: 5168

South Asian (SAS) AF: 0.851 AC: 4099 AN: 4818

European-Finnish (FIN) AF: 0.837 AC: 8848 AN: 10572

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53628 AN: 68008

Other (OTH) AF: 0.769 AC: 1619 AN: 2106

Alfa AF: 0.785 Hom.: 78849

Bravo AF: 0.757

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.080
DANN	Benign	0.37
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2758352; hg19: chr6-160122921;