chr5-114362941-G-GCCT
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_021614.4(KCNN2):c.804_805insTCC(p.Ala268_Ala269insSer) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNN2
NM_021614.4 inframe_insertion
NM_021614.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.57
Genes affected
KCNN2 (HGNC:6291): (potassium calcium-activated channel subfamily N member 2) Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP3
?
Nonframeshift variant in repetitive region in NM_021614.4
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNN2 | NM_021614.4 | c.804_805insTCC | p.Ala268_Ala269insSer | inframe_insertion | 1/8 | ENST00000673685.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNN2 | ENST00000673685.1 | c.804_805insTCC | p.Ala268_Ala269insSer | inframe_insertion | 1/8 | NM_021614.4 | P2 | ||
KCNN2 | ENST00000512097.10 | c.1002_1003insTCC | p.Ala334_Ala335insSer | inframe_insertion | 6/13 | 5 | A2 | ||
KCNN2 | ENST00000631899.2 | c.206_207insTCC | p.Ala69_Ala70insSer | inframe_insertion | 1/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151966Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1433512Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 712574
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151966Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74228
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is not observed in the gnomAD v2.1.1 dataset. Inframe insertion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at