Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001243340 | SCV001416491 | pathogenic | LAMA2-related muscular dystrophy | 2023-08-04 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 38 of the LAMA2 gene. It does not directly change the encoded amino acid sequence of the LAMA2 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of LAMA2-related muscular dystrophy (PMID: 12552556; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS37+5G>A. ClinVar contains an entry for this variant (Variation ID: 968246). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 38, but is expected to preserve the integrity of the reading-frame (PMID: 12552556). This variant disrupts the c.5562+5 nucleotide in the LAMA2 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 9536098, 10611118, 12552556, 17576681, 20207543). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |