Genetic Variant SOD2:p.Val16Asp (chr6-159692840-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000636.4(SOD2):c.47T>A(p.Val16Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V16A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOD2
NM_000636.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Publications

0 publications found

Variant links:

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

SOD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18468991).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SOD2	NM_000636.4	MANE Select	c.47T>A	p.Val16Asp	missense	Exon 2 of 5	NP_000627.2
SOD2	NM_001024465.3		c.47T>A	p.Val16Asp	missense	Exon 2 of 6	NP_001019636.1
SOD2	NM_001024466.3		c.47T>A	p.Val16Asp	missense	Exon 2 of 5	NP_001019637.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SOD2	ENST00000538183.7	TSL:1 MANE Select	c.47T>A	p.Val16Asp	missense	Exon 2 of 5	ENSP00000446252.1
SOD2	ENST00000367055.8	TSL:1	c.47T>A	p.Val16Asp	missense	Exon 2 of 6	ENSP00000356022.4
SOD2	ENST00000452684.2	TSL:1	c.47T>A	p.Val16Asp	missense	Exon 2 of 2	ENSP00000406713.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725712

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110986

Other (OTH)

AF:

0.00

AC:

AN:

60284

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.041

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.37

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

PhyloP100

2.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

REVEL

Benign

0.12

Sift

Benign

0.055

Sift4G

Benign

0.096

Polyphen

0.96

Vest4

0.21

MutPred

0.58

Gain of disorder (P = 0.009)

MVP

0.29

MPC

0.80

ClinPred

0.19

GERP RS

3.1

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.50

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over