NM_000238.4:c.2405A>G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_000238.4(KCNH2):c.2405A>G(p.Asn802Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,740 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 (★★).
Frequency
Consequence
NM_000238.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.2405A>G | p.Asn802Ser | missense_variant | Exon 10 of 15 | ENST00000262186.10 | NP_000229.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.2405A>G | p.Asn802Ser | missense_variant | Exon 10 of 15 | 1 | NM_000238.4 | ENSP00000262186.5 | ||
KCNH2 | ENST00000330883.9 | c.1385A>G | p.Asn462Ser | missense_variant | Exon 6 of 11 | 1 | ENSP00000328531.4 | |||
KCNH2 | ENST00000684241.1 | n.3238A>G | non_coding_transcript_exon_variant | Exon 8 of 13 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461740Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727192
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
- -
Long QT syndrome Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 802 of the KCNH2 protein (p.Asn802Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with long QT Syndrome (internal data). ClinVar contains an entry for this variant (Variation ID: 216326). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Cardiovascular phenotype Uncertain:1
- -
Short QT syndrome type 1;C3150943:Long QT syndrome 2 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at