rs72549419
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000238.4(KCNH2):c.77-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,589,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000238.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.77-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.77-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000238.4 | P1 | |||
KCNH2 | ENST00000532957.5 | n.300-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000464 AC: 1AN: 215648Hom.: 0 AF XY: 0.00000846 AC XY: 1AN XY: 118228
GnomAD4 exome AF: 0.0000153 AC: 22AN: 1437100Hom.: 0 Cov.: 33 AF XY: 0.0000140 AC XY: 10AN XY: 712888
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Long QT syndrome Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Mar 26, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 02, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2024 | The c.77-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 2 in the KCNH2 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear. - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at