21-34370501-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_172201.2(KCNE2):c.23C>T(p.Thr8Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T8A) has been classified as Benign.
Frequency
Consequence
NM_172201.2 missense
Scores
Clinical Significance
Conservation
Publications
- familial atrial fibrillationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- long QT syndrome 6Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
- long QT syndromeInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNE2 | NM_172201.2 | c.23C>T | p.Thr8Ile | missense_variant | Exon 2 of 2 | ENST00000290310.4 | NP_751951.1 | |
LOC105372791 | NR_188571.1 | n.786G>A | non_coding_transcript_exon_variant | Exon 2 of 3 | ||||
LOC105372791 | NR_188572.1 | n.786G>A | non_coding_transcript_exon_variant | Exon 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251326 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727246 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74344 show subpopulations
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
The p.T8I variant (also known as c.23C>T), located in coding exon 1 of the KCNE2 gene, results from a C to T substitution at nucleotide position 23. The threonine at codon 8 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at