rs2070994

Variant names:

• chr6-159688019-A-T
• rs2070994
• NM_000636.4:c.343+107T>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.343+107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 723,186 control chromosomes in the GnomAD database, including 76,882 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 0.40 (13610 hom., cov: 31)
  • Exomes 𝑓: 0.46 (63272 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.343+107T>A		intron_variant	Intron 3 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.343+107T>A		intron_variant	Intron 3 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61143 AN: 151766 Hom.: 13600 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.458 AC: 261759 AN: 571300 Hom.: 63272 AF XY: 0.459 AC XY: 141199 AN XY: 307292

African (AFR) AF: 0.220 AC: 3232 AN: 14678

American (AMR) AF: 0.562 AC: 16643 AN: 29618

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 7294 AN: 15940

East Asian (EAS) AF: 0.122 AC: 4174 AN: 34208

South Asian (SAS) AF: 0.480 AC: 26942 AN: 56184

European-Finnish (FIN) AF: 0.473 AC: 20945 AN: 44274

Middle Eastern (MID) AF: 0.398 AC: 1481 AN: 3720

European-Non Finnish (NFE) AF: 0.489 AC: 167842 AN: 342962

Other (OTH) AF: 0.444 AC: 13206 AN: 29716

GnomAD4 genome AF: 0.403 AC: 61151 AN: 151886 Hom.: 13610 Cov.: 31 AF XY: 0.400 AC XY: 29707 AN XY: 74232

African (AFR) AF: 0.223 AC: 9245 AN: 41434

American (AMR) AF: 0.488 AC: 7435 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3468

East Asian (EAS) AF: 0.133 AC: 686 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2301 AN: 4826

European-Finnish (FIN) AF: 0.462 AC: 4863 AN: 10516

Middle Eastern (MID) AF: 0.413 AC: 119 AN: 288

European-Non Finnish (NFE) AF: 0.494 AC: 33526 AN: 67924

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.456 Hom.: 2063

Bravo AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.82
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: rs2070994; hg19: chr6-160109051; COSMIC: COSV61622898; COSMIC: COSV61622898;