1-196236032-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_198503.5(KCNT2):c.3250C>T(p.Leu1084=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000154 in 1,603,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
KCNT2
NM_198503.5 synonymous
NM_198503.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.05
Genes affected
KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
Variant 1-196236032-G-A is Benign according to our data. Variant chr1-196236032-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048030.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000099 (15/151478) while in subpopulation SAS AF= 0.0029 (14/4822). AF 95% confidence interval is 0.00175. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT2 | NM_198503.5 | c.3250C>T | p.Leu1084= | synonymous_variant | 27/28 | ENST00000294725.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT2 | ENST00000294725.14 | c.3250C>T | p.Leu1084= | synonymous_variant | 27/28 | 1 | NM_198503.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000991 AC: 15AN: 151360Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000372 AC: 93AN: 250132Hom.: 2 AF XY: 0.000510 AC XY: 69AN XY: 135278
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GnomAD4 exome AF: 0.000160 AC: 232AN: 1452488Hom.: 1 Cov.: 26 AF XY: 0.000239 AC XY: 173AN XY: 723124
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GnomAD4 genome ? AF: 0.0000990 AC: 15AN: 151478Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74066
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KCNT2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 16, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at