rs12673992
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_012281.3(KCND2):c.1116-134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 657,464 control chromosomes in the GnomAD database, including 37,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.39 ( 14667 hom., cov: 32)
Exomes 𝑓: 0.29 ( 23303 hom. )
Consequence
KCND2
NM_012281.3 intron
NM_012281.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.325
Genes affected
KCND2 (HGNC:6238): (potassium voltage-gated channel subfamily D member 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. 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, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 7-120732769-A-G is Benign according to our data. Variant chr7-120732769-A-G is described in ClinVar as [Benign]. Clinvar id is 1241406.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCND2 | NM_012281.3 | c.1116-134A>G | intron_variant | ENST00000331113.9 | NP_036413.1 | |||
KCND2 | XM_047420346.1 | c.1116-134A>G | intron_variant | XP_047276302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCND2 | ENST00000331113.9 | c.1116-134A>G | intron_variant | 1 | NM_012281.3 | ENSP00000333496 | P1 |
Frequencies
GnomAD3 genomes AF: 0.393 AC: 59686AN: 151880Hom.: 14611 Cov.: 32
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GnomAD4 exome AF: 0.286 AC: 144433AN: 505466Hom.: 23303 AF XY: 0.279 AC XY: 75568AN XY: 270986
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GnomAD4 genome AF: 0.394 AC: 59816AN: 151998Hom.: 14667 Cov.: 32 AF XY: 0.395 AC XY: 29315AN XY: 74290
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at