chr6-159693540-G-T

Variant names:

• chr6-159693540-G-T
• rs2758343
• ENST00000545162.5:c.93-677C>A

Variant summary

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

The ENST00000545162.5(SOD2):​c.93-677C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,004 control chromosomes in the GnomAD database, including 16,037 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 0.45 (16037 hom., cov: 33)
• Consequence: SOD2 ENST00000545162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743
• Publications: 4 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545162.5. 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.-115-677C>A		intron	N/A	NP_001309746.1
	SOD2	NM_001322819.2		c.-115-677C>A		intron	N/A	NP_001309748.1
	SOD2	NM_001322820.2		c.-115-677C>A		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.93-677C>A		intron	N/A	ENSP00000441362.1
	SOD2	ENST00000535561.5	TSL:3	c.93-677C>A		intron	N/A	ENSP00000445015.1
	SOD2	ENST00000546087.5	TSL:2	c.-115-677C>A		intron	N/A	ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68327 AN: 151888 Hom.: 16024 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.450 AC: 68364 AN: 152004 Hom.: 16037 Cov.: 33 AF XY: 0.446 AC XY: 33116 AN XY: 74294

African (AFR) AF: 0.356 AC: 14767 AN: 41488

American (AMR) AF: 0.528 AC: 8069 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3470

East Asian (EAS) AF: 0.143 AC: 737 AN: 5164

South Asian (SAS) AF: 0.511 AC: 2458 AN: 4814

European-Finnish (FIN) AF: 0.466 AC: 4915 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34083 AN: 67914

Other (OTH) AF: 0.452 AC: 953 AN: 2108

Alfa AF: 0.356 Hom.: 1028

Bravo AF: 0.448

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		0.74
PromoterAI		-0.028	Neutral
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: rs2758343; hg19: chr6-160114572;