rs989125451
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006440.5(TXNRD2):c.860T>G(p.Leu287Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L287L) has been classified as Likely benign.
Frequency
Consequence
NM_006440.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.860T>G | p.Leu287Arg | missense_variant | 11/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.860T>G | p.Leu287Arg | missense_variant | 11/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249160Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135206
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461640Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727118
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 14, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 407096). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 287 of the TXNRD2 protein (p.Leu287Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at