Submissions for variant NM_000426.4(LAMA2):c.9227_9243dup (p.Ile3082delinsLeuAlaTer)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratorio De Medicina Genomica, Universidad Icesi	RCV003231060	SCV003927996	likely pathogenic	Merosin deficient congenital muscular dystrophy	2023-05-31	criteria provided, single submitter	clinical testing	This genetic variant alters the reading frame by duplicating a fragment of 17 base pairs, specifically in the isoleucine residue 3082, causing a stop codon 3 amino acids later (p.Ile3082Leufs*3) in the LAMA2 gene. While the frameshift variant confirmed in this patient is not anticipated to result in nonsense mediated decay, it is expected to lack the last 39 residues of the LAMA2 protein. The most frequently reported pathogenic genotypes in the LAMA2 gene are variants that create a premature termination codon, despite the location throughout the gene, such as the present variant. This variant is not reported in population databases such as gnomAD, 1000 genomes and HGMD. This premature translational stop signal has been observed in an individual with Congenital muscular dystrophy type 1A (CMD1A). Other variants that disrupt this protein region have been observed in individuals with LAMA2-related conditions (PMID: 20207543 and PMID: 11591858). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.