rs41314677
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_172201.2(KCNE2):c.-12-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,000 control chromosomes in the GnomAD database, including 2,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.073 ( 777 hom., cov: 33)
Exomes 𝑓: 0.036 ( 1477 hom. )
Consequence
KCNE2
NM_172201.2 splice_polypyrimidine_tract, intron
NM_172201.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.146
Genes affected
KCNE2 (HGNC:6242): (potassium voltage-gated channel subfamily E regulatory subunit 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a small integral membrane subunit that assembles with the KCNH2 gene product, a pore-forming protein, to alter its function. This gene is expressed in heart and muscle and the gene mutations are associated with cardiac arrhythmia. [provided by RefSeq, Jul 2008]
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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=-0.79).
BP6
?
Variant 21-34370451-A-G is Benign according to our data. Variant chr21-34370451-A-G is described in ClinVar as [Benign]. Clinvar id is 262799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-34370451-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE2 | NM_172201.2 | c.-12-16A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000290310.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE2 | ENST00000290310.4 | c.-12-16A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_172201.2 | P1 | |||
ENST00000440403.2 | n.838T>C | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0730 AC: 11101AN: 152148Hom.: 768 Cov.: 33
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GnomAD3 exomes AF: 0.0365 AC: 9133AN: 250390Hom.: 403 AF XY: 0.0349 AC XY: 4739AN XY: 135672
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GnomAD4 exome AF: 0.0361 AC: 52789AN: 1461734Hom.: 1477 Cov.: 31 AF XY: 0.0360 AC XY: 26171AN XY: 727182
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GnomAD4 genome ? AF: 0.0731 AC: 11132AN: 152266Hom.: 777 Cov.: 33 AF XY: 0.0698 AC XY: 5200AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
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