rs369314508
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000238.4(KCNH2):c.432C>T(p.Asp144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
KCNH2
NM_000238.4 synonymous
NM_000238.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.13
Genes affected
KCNH2 (HGNC:6251): (potassium voltage-gated channel subfamily H member 2) This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 7-150959612-G-A is Benign according to our data. Variant chr7-150959612-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 413339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.13 with no splicing effect.
BS2
?
High AC in GnomAd4 at 28 AD,Digenic gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.432C>T | p.Asp144= | synonymous_variant | 3/15 | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.432C>T | p.Asp144= | synonymous_variant | 3/15 | 1 | NM_000238.4 | P1 | |
KCNH2 | ENST00000532957.5 | n.655C>T | non_coding_transcript_exon_variant | 3/9 | 2 | ||||
KCNH2 | ENST00000684241.1 | n.1265C>T | non_coding_transcript_exon_variant | 1/13 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251166Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135802
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727230
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 18, 2017 | 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 | Jan 14, 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. - |
KCNH2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 10, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 11, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at