rs759887868
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000238.4(KCNH2):c.2967C>T(p.Gly989=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,593,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G989G) has been classified as Likely benign.
Frequency
Consequence
NM_000238.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.2967C>T | p.Gly989= | splice_region_variant, synonymous_variant | 13/15 | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.2967C>T | p.Gly989= | splice_region_variant, synonymous_variant | 13/15 | 1 | NM_000238.4 | P1 | |
KCNH2 | ENST00000330883.9 | c.1947C>T | p.Gly649= | splice_region_variant, synonymous_variant | 9/11 | 1 | |||
KCNH2 | ENST00000684241.1 | n.3800C>T | splice_region_variant, non_coding_transcript_exon_variant | 11/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000137 AC: 29AN: 211590Hom.: 0 AF XY: 0.000113 AC XY: 13AN XY: 115062
GnomAD4 exome AF: 0.0000229 AC: 33AN: 1441668Hom.: 0 Cov.: 36 AF XY: 0.0000224 AC XY: 16AN XY: 715338
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74474
ClinVar
Submissions by phenotype
Long QT syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 17, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at