6-159679084-A-T

Variant names:

• chr6-159679084-A-T
• rs2842980
• NM_000636.4:c.*3409T>A

Variant summary

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

The NM_000636.4(SOD2):​c.*3409T>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 0.767 in 152,142 control chromosomes in the GnomAD database, including 45,174 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 (45174 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 36 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.*3409T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.*3409T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116563 AN: 152024 Hom.: 45145 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.778

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.767 AC: 116638 AN: 152142 Hom.: 45174 Cov.: 33 AF XY: 0.768 AC XY: 57145 AN XY: 74388

African (AFR) AF: 0.700 AC: 29028 AN: 41460

American (AMR) AF: 0.830 AC: 12686 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2629 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2784 AN: 5174

South Asian (SAS) AF: 0.852 AC: 4117 AN: 4830

European-Finnish (FIN) AF: 0.836 AC: 8861 AN: 10594

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

European-Non Finnish (NFE) AF: 0.795 AC: 54093 AN: 68008

Other (OTH) AF: 0.773 AC: 1635 AN: 2116

Alfa AF: 0.787 Hom.: 5894

Bravo AF: 0.760

Asia WGS AF: 0.687 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.30
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs2842980; hg19: chr6-160100116;