10-77637586-TCCGCCGCCGCCGCCG-TCCGCCGCCGCCGCCGCCGCCG
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001161352.2(KCNMA1):c.51_56dupCGGCGG(p.Gly18_Gly19dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000997 in 1,524,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000093 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
KCNMA1
NM_001161352.2 disruptive_inframe_insertion
NM_001161352.2 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.59
Genes affected
KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000926 AC: 14AN: 151112Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000100 AC: 138AN: 1373640Hom.: 0 Cov.: 31 AF XY: 0.0000974 AC XY: 66AN XY: 677456
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GnomAD4 genome AF: 0.0000926 AC: 14AN: 151112Hom.: 0 Cov.: 32 AF XY: 0.0000813 AC XY: 6AN XY: 73764
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 12, 2023 | In-frame duplication of 2 amino acids in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge - |
Generalized epilepsy-paroxysmal dyskinesia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 20, 2024 | This variant, c.51_56dup, results in the insertion of 2 amino acid(s) of the KCNMA1 protein (p.Gly19_Gly20dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KCNMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 638907). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Epilepsy, idiopathic generalized, susceptibility to, 16;C5574945:Generalized epilepsy-paroxysmal dyskinesia syndrome Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Brain Gene Registry | - | Variant interpreted as Uncertain significance and reported on 07-25-2022 by Invitae . Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Philip Payne PhD, FACMI from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at