GeneBe

22-19875633-TGG-TGGGG

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006440.5(TXNRD2):​c.*238_*239dupCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TXNRD2
NM_006440.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

2 publications found
Variant links:
Genes affected
TXNRD2 (HGNC:18155): (thioredoxin reductase 2) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]
TXNRD2 Gene-Disease associations (from GenCC):
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • familial glucocorticoid deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • dilated cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • glucocorticoid deficiency 5
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TXNRD2NM_006440.5 linkc.*238_*239dupCC 3_prime_UTR_variant Exon 18 of 18 ENST00000400521.7 NP_006431.2 Q9NNW7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TXNRD2ENST00000400521.7 linkc.*238_*239dupCC 3_prime_UTR_variant Exon 18 of 18 1 NM_006440.5 ENSP00000383365.1 Q9NNW7-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
166
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130
African (AFR)
AF:
0.00
AC:
0
AN:
10
American (AMR)
AF:
0.00
AC:
0
AN:
2
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
136
Other (OTH)
AF:
0.00
AC:
0
AN:
6
GnomAD4 genome
Cov.:
23
Alfa
AF:
0.00
Hom.:
38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.0
Mutation Taster
=100/0
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs59339361; hg19: chr22-19863156; API