Submissions for variant NM_001161352.2(KCNMA1):c.2484+7G>A

gnomAD frequency: 0.00176  dbSNP: rs13377017

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000639898	SCV000761484	benign	Generalized epilepsy-paroxysmal dyskinesia syndrome	2025-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000729892	SCV000857588	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224360	SCV003920102	likely benign	Generalized epilepsy-paroxysmal dyskinesia syndrome; Cerebellar atrophy, developmental delay, and seizures; Epilepsy, idiopathic generalized, susceptibility to, 16; Liang-Wang syndrome	2022-05-26	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.5% (243/41436) (https://gnomad.broadinstitute.org/variant/10-76953794-C-T?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Benign (Variation ID:532948). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Splice prediction tools suggest that this variant may not affect splicing. Further studies are needed to understand its impact. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000729892	SCV005204552	likely benign	not specified	2024-06-20	criteria provided, single submitter	clinical testing	Variant summary: KCNMA1 c.2484+7G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00035 in 251302 control chromosomes, predominantly at a frequency of 0.0051 within the African or African-American subpopulation in the gnomAD database, suggesting the variant may be benign. To our knowledge, no occurrence of c.2484+7G>A in individuals affected with Paroxysmal Nonkinesigenic Dyskinesia, 3, With Or Without Generalized Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 532948). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004547798	SCV004766402	likely benign	KCNMA1-related disorder	2022-10-25	no assertion criteria provided	clinical testing	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).