chr5-114362921-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_021614.4(KCNN2):c.782C>G(p.Pro261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,572,238 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
KCNN2
NM_021614.4 missense
NM_021614.4 missense
Scores
2
4
8
Clinical Significance
Conservation
PhyloP100: 3.10
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 Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19030026).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNN2 | NM_021614.4 | c.782C>G | p.Pro261Arg | missense_variant | 1/8 | ENST00000673685.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNN2 | ENST00000673685.1 | c.782C>G | p.Pro261Arg | missense_variant | 1/8 | NM_021614.4 | P2 | ||
KCNN2 | ENST00000512097.10 | c.980C>G | p.Pro327Arg | missense_variant | 6/13 | 5 | A2 | ||
KCNN2 | ENST00000631899.2 | c.185C>G | p.Pro62Arg | missense_variant | 1/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000220 AC: 3AN: 136364Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000103 AC: 2AN: 194416Hom.: 0 AF XY: 0.0000186 AC XY: 2AN XY: 107642
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GnomAD4 exome AF: 0.00000348 AC: 5AN: 1435766Hom.: 0 Cov.: 78 AF XY: 0.00000560 AC XY: 4AN XY: 713942
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GnomAD4 genome ? AF: 0.0000220 AC: 3AN: 136472Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 1AN XY: 66056
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | KCNN2: PP3 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Polyphen
0.43
.;B
Vest4
0.35
MutPred
0.28
.;Loss of loop (P = 0.0073);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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