rs371509270
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000330883.9(KCNH2):c.-4C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,543,936 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
KCNH2
ENST00000330883.9 5_prime_UTR
ENST00000330883.9 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0970
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 7-150955507-G-A is Benign according to our data. Variant chr7-150955507-G-A is described in ClinVar as [Benign]. Clinvar id is 200218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-150955507-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00268 (408/152370) while in subpopulation AFR AF= 0.00952 (396/41592). AF 95% confidence interval is 0.00875. There are 1 homozygotes in gnomad4. There are 217 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 408 AD,Digenic gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.1128+1784C>T | intron_variant | ENST00000262186.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.1128+1784C>T | intron_variant | 1 | NM_000238.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00269 AC: 409AN: 152252Hom.: 1 Cov.: 34
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GnomAD3 exomes AF: 0.000464 AC: 67AN: 144476Hom.: 0 AF XY: 0.000451 AC XY: 35AN XY: 77540
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GnomAD4 exome AF: 0.000231 AC: 321AN: 1391566Hom.: 1 Cov.: 31 AF XY: 0.000196 AC XY: 134AN XY: 685316
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GnomAD4 genome ? AF: 0.00268 AC: 408AN: 152370Hom.: 1 Cov.: 34 AF XY: 0.00291 AC XY: 217AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2014 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 07, 2018 | - - |
Cardiac arrhythmia Benign:1
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 29, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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