6-159692289-C-T

Variant names:

• chr6-159692289-C-T
• rs2842960
• ENST00000452684.2:c.*175G>A

Variant summary

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

The NM_001322816.2(SOD2):​c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 724,018 control chromosomes in the GnomAD database, including 85,733 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 0.47 (17298 hom., cov: 31)
  • Exomes 𝑓: 0.48 (68435 hom.)
• Consequence: SOD2 NM_001322816.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322816.2. 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.226+372G>A		intron	N/A	NP_000627.2	P04179-1
	SOD2	NM_001322816.2		c.*175G>A		3_prime_UTR	Exon 2 of 2	NP_001309745.1	G5E9P6
	SOD2	NM_001024465.3		c.226+372G>A		intron	N/A	NP_001019636.1	P04179-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000452684.2	TSL:1	c.*175G>A		3_prime_UTR	Exon 2 of 2	ENSP00000406713.2	G5E9P6
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.226+372G>A		intron	N/A	ENSP00000446252.1	P04179-1
	SOD2	ENST00000367055.8	TSL:1	c.226+372G>A		intron	N/A	ENSP00000356022.4	P04179-1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71530 AN: 151914 Hom.: 17282 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.480 AC: 274674 AN: 571984 Hom.: 68435 Cov.: 8 AF XY: 0.481 AC XY: 134842 AN XY: 280566

African (AFR) AF: 0.427 AC: 5621 AN: 13166

American (AMR) AF: 0.574 AC: 4648 AN: 8104

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 5747 AN: 11422

East Asian (EAS) AF: 0.128 AC: 3129 AN: 24386

South Asian (SAS) AF: 0.524 AC: 6663 AN: 12706

European-Finnish (FIN) AF: 0.481 AC: 12541 AN: 26074

Middle Eastern (MID) AF: 0.445 AC: 1007 AN: 2264

European-Non Finnish (NFE) AF: 0.498 AC: 222575 AN: 446718

Other (OTH) AF: 0.469 AC: 12743 AN: 27144

GnomAD4 genome AF: 0.471 AC: 71575 AN: 152034 Hom.: 17298 Cov.: 31 AF XY: 0.466 AC XY: 34609 AN XY: 74312

African (AFR) AF: 0.426 AC: 17662 AN: 41464

American (AMR) AF: 0.537 AC: 8205 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1796 AN: 3462

East Asian (EAS) AF: 0.143 AC: 739 AN: 5174

South Asian (SAS) AF: 0.513 AC: 2471 AN: 4816

European-Finnish (FIN) AF: 0.466 AC: 4918 AN: 10560

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34203 AN: 67964

Other (OTH) AF: 0.473 AC: 998 AN: 2110

Alfa AF: 0.496 Hom.: 9158

Bravo AF: 0.472

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		-0.017
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs2842960; hg19: chr6-160113321; COSMIC: COSV61623443; COSMIC: COSV61623443;