chr8-98428784-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_020697.4(KCNS2):c.805G>A(p.Val269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,614,126 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 4 hom. )
Consequence
KCNS2
NM_020697.4 missense
NM_020697.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 2.56
Genes affected
KCNS2 (HGNC:6301): (potassium voltage-gated channel modifier subfamily S member 2) Predicted to enable voltage-gated potassium channel activity. Predicted to be involved in potassium ion transmembrane transport and regulation of delayed rectifier potassium channel activity. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be part of voltage-gated potassium channel complex. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
STK3 (HGNC:11406): (serine/threonine kinase 3) This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012956023).
BP6
?
Variant 8-98428784-G-A is Benign according to our data. Variant chr8-98428784-G-A is described in ClinVar as [Benign]. Clinvar id is 723919.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNS2 | NM_020697.4 | c.805G>A | p.Val269Ile | missense_variant | 2/2 | ENST00000287042.5 | |
STK3 | XM_047422133.1 | c.1423+8319C>T | intron_variant | ||||
STK3 | XR_007060752.1 | n.1571+8319C>T | intron_variant, non_coding_transcript_variant | ||||
STK3 | XR_007060753.1 | n.1571+8319C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNS2 | ENST00000287042.5 | c.805G>A | p.Val269Ile | missense_variant | 2/2 | 1 | NM_020697.4 | P1 | |
KCNS2 | ENST00000521839.1 | c.805G>A | p.Val269Ile | missense_variant | 2/2 | 5 | P1 | ||
STK3 | ENST00000517832.1 | n.483+5343C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
STK3 | ENST00000649151.1 | n.427+5343C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00203 AC: 309AN: 152114Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000577 AC: 145AN: 251496Hom.: 2 AF XY: 0.000486 AC XY: 66AN XY: 135922
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GnomAD4 exome AF: 0.000209 AC: 305AN: 1461892Hom.: 4 Cov.: 32 AF XY: 0.000177 AC XY: 129AN XY: 727246
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GnomAD4 genome ? AF: 0.00202 AC: 308AN: 152234Hom.: 2 Cov.: 32 AF XY: 0.00184 AC XY: 137AN XY: 74424
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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 | Invitae | Jul 13, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Uncertain
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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