ClinVar Miner

Submissions for variant NM_032108.4(SEMA6B):c.1991del (p.Gly664fs)

dbSNP: rs1443687532
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Tgen's Center For Rare Childhood Disorders, Translational Genomics Research Institute (TGEN) RCV001093613 SCV002061353 likely pathogenic Epilepsy, progressive myoclonic, 11 2022-01-20 criteria provided, single submitter research This variant was identified in a female with global developmental delay, seizures, hypotonia, muscle weakness, microcephaly, and facial dysmorphism. The variant causes a frameshift changing a Glycine into an Alanine at amino acid 664. This causes a premature stop codon at position 21 of the reading frame (p.Gly664AlafsX21). The variant is not found in gnomAD genomes. We classify this variant as likely pathogenic based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PVS1, PM2).
Illumina Laboratory Services, Illumina RCV003127629 SCV003802804 pathogenic not provided 2022-09-22 criteria provided, single submitter clinical testing The SEMA6B c.1991del (p.Gly664AlafsTer21) variant results in the deletion of a nucleotide at position c.1991, causing a shift in the protein reading frame. This variant occurs in the last exon of the gene and may escape nonsense-mediated mRNA decay and could result in a truncated protein lacking the important intracellular domain (ICD). The c.1991del variant has been reported in a de novo heterozygous state in three unrelated individuals with epilepsy, developmental delay and regression, intellectual disability, ataxia, and tremor (PMID: 32169168; PMID: 35604360). This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.1991del (p.Gly664AlafsTer21) variant is classified as pathogenic for SEMA6B-related progressive myoclonic epilepsy.
Institute of Human Genetics, University of Leipzig Medical Center RCV001093613 SCV004242457 pathogenic Epilepsy, progressive myoclonic, 11 2023-12-14 criteria provided, single submitter clinical testing Criteria applied: PVS1_STR,PS2,PS4_SUP,PM2_SUP
OMIM RCV001093613 SCV001250717 pathogenic Epilepsy, progressive myoclonic, 11 2020-05-12 no assertion criteria provided literature only

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