Genetic Variant TXNRD2:n.1908delC (chr22-19875633-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006440.5(TXNRD2):c.*239delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,008 control chromosomes in the GnomAD database, including 9,860 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 9856 hom., cov: 23)

Exomes 𝑓: 0.20 ( 4 hom. )

Consequence

TXNRD2
NM_006440.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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)

TXNRD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 22-19875633-TG-T is Benign according to our data. Variant chr22-19875633-TG-T is described in ClinVar as [Benign]. Clinvar id is 1239595.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD2	NM_006440.5 link	c.*239delC		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
TXNRD2	ENST00000400521.7 link	c.*239delC		3_prime_UTR_variant	Exon 18 of 18	1	NM_006440.5	ENSP00000383365.1		Q9NNW7-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43390

AN:

150730

Hom.:

9810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.200

AC:

AN:

160

Hom.:

Cov.:

AF XY:

0.211

AC XY:

AN XY:

128

show subpopulations

African (AFR)

AF:

0.600

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.177

AC:

AN:

130

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.288

AC:

43505

AN:

150848

Hom.:

9856

Cov.:

AF XY:

0.283

AC XY:

20839

AN XY:

73642

show subpopulations

African (AFR)

AF:

0.632

AC:

26100

AN:

41290

American (AMR)

AF:

0.201

AC:

3054

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

749

AN:

3444

East Asian (EAS)

AF:

0.0329

AC:

169

AN:

5132

South Asian (SAS)

AF:

0.186

AC:

882

AN:

4736

European-Finnish (FIN)

AF:

0.0959

AC:

990

AN:

10328

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.160

AC:

10823

AN:

67472

Other (OTH)

AF:

0.253

AC:

526

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1252

2505

3757

5010

6262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0435

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(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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22-19875633-TGG-TG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over