6-159688512-GGAAAT-GGAAATGAAAT

Variant names:

• chr6-159688514-AAA-AAATGA
• NM_000636.4:c.227-277_227-275dupTCA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000636.4(SOD2):​c.227-277_227-275dupTCA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.227-277_227-275dupTCA		intron	N/A	NP_000627.2	P04179-1
	SOD2	NM_001024465.3		c.227-277_227-275dupTCA		intron	N/A	NP_001019636.1	P04179-1
	SOD2	NM_001024466.3		c.227-3486_227-3484dupTCA		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.227-275_227-274insTCA		intron	N/A	ENSP00000446252.1	P04179-1
	SOD2	ENST00000367055.8	TSL:1	c.227-275_227-274insTCA		intron	N/A	ENSP00000356022.4	P04179-1
	SOD2	ENST00000881541.1		c.227-278_227-277insTCA		intron	N/A	ENSP00000551600.1

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.059

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-160109546;