rs763135225
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_004974.4(KCNA2):āc.318A>Gā(p.Leu106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,064 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
KCNA2
NM_004974.4 synonymous
NM_004974.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.75
Genes affected
KCNA2 (HGNC:6220): (potassium voltage-gated channel subfamily A member 2) Potassium 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 1-110604465-T-C is Benign according to our data. Variant chr1-110604465-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476052.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.75 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000394 (6/152188) while in subpopulation AFR AF= 0.000145 (6/41424). AF 95% confidence interval is 0.0000629. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNA2 | NM_004974.4 | c.318A>G | p.Leu106= | synonymous_variant | 3/3 | ENST00000316361.10 | NP_004965.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNA2 | ENST00000316361.10 | c.318A>G | p.Leu106= | synonymous_variant | 3/3 | 2 | NM_004974.4 | ENSP00000314520 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251390Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461876Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727238
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 32 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 11, 2022 | - - |
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