rs1800706

Variant names:

• chr22-19940499-G-A
• rs1800706
• NM_006440.5:c.103+1202C>T

Variant summary

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

The NM_006440.5(TXNRD2):​c.103+1202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,014 control chromosomes in the GnomAD database, including 4,122 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 0.22 (4122 hom., cov: 31)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 4 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.103+1202C>T		intron_variant	Intron 1 of 17	ENST00000400521.7	NP_006431.2
TXNRD2	NM_001352300.2	c.103+1202C>T		intron_variant	Intron 1 of 16		NP_001339229.1
TXNRD2	NM_001282512.3	c.103+1202C>T		intron_variant	Intron 1 of 11		NP_001269441.1
TXNRD2	NR_147957.2	n.118+1202C>T		intron_variant	Intron 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.103+1202C>T		intron_variant	Intron 1 of 17	1	NM_006440.5	ENSP00000383365.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33272 AN: 151896 Hom.: 4120 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33274 AN: 152014 Hom.: 4122 Cov.: 31 AF XY: 0.218 AC XY: 16187 AN XY: 74298

African (AFR) AF: 0.103 AC: 4252 AN: 41476

American (AMR) AF: 0.213 AC: 3259 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1475 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1425 AN: 5156

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2004 AN: 10536

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18826 AN: 67966

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.267 Hom.: 9254

Bravo AF: 0.212

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		0.25
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: rs1800706; hg19: chr22-19928022;