rs372029645
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000238.4(KCNH2):c.36C>T(p.Asn12=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000498 in 1,606,328 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 0.000013 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
KCNH2
NM_000238.4 synonymous
NM_000238.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.17
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 7-150977878-G-A is Benign according to our data. Variant chr7-150977878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 413321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNH2 | NM_000238.4 | c.36C>T | p.Asn12= | synonymous_variant | 1/15 | ENST00000262186.10 | |
KCNH2 | NM_172056.3 | c.36C>T | p.Asn12= | synonymous_variant | 1/9 | ||
KCNH2 | NR_176254.1 | n.444C>T | non_coding_transcript_exon_variant | 1/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNH2 | ENST00000262186.10 | c.36C>T | p.Asn12= | synonymous_variant | 1/15 | 1 | NM_000238.4 | P1 | |
KCNH2 | ENST00000532957.5 | n.259C>T | non_coding_transcript_exon_variant | 1/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 149952Hom.: 0 Cov.: 27
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GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239550Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131736
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GnomAD4 exome AF: 0.00000412 AC: 6AN: 1456262Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2AN XY: 724342
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GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150066Hom.: 0 Cov.: 27 AF XY: 0.0000273 AC XY: 2AN XY: 73246
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
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 | Dec 12, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 01, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2020 | 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 | Mar 18, 2020 | - - |
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