ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.4876C>T (p.Gln1626Ter)

gnomAD frequency: 0.00002  dbSNP: rs369776766
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000536256 SCV000658692 pathogenic LAMA2-related muscular dystrophy 2023-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1626*) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). This variant is present in population databases (rs369776766, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 477476). For these reasons, this variant has been classified as Pathogenic.
New York Genome Center RCV002227483 SCV002506725 likely pathogenic Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23 2021-06-22 criteria provided, single submitter clinical testing The heterozygous c.4876C>T (p.Gln1626Ter) stop-gained variant identified in exon 34 (of 65) of the LAMA2 gene has not been reported in affected individuals in theliterature. The variant creates a premature translation termination codon and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant has been reported in the ClinVar database [Variation ID: 477476]. The variant has 0.00001971 allele frequency in the gnomAD(v3) database (3 out of 152206 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. Based on the available evidence, the heterozygous c.4876C>T (p.Gln1626Ter) stop-gained variant identified in the LAMA2 gene is reported as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000536256 SCV002766030 pathogenic LAMA2-related muscular dystrophy 2024-10-31 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.4876C>T (p.Gln1626X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 250824 control chromosomes. To our knowledge, no occurrence of c.4876C>T in individuals affected with Laminin Alpha 2-Related Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 477476). Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV003470796 SCV004190457 likely pathogenic Merosin deficient congenital muscular dystrophy 2024-03-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002227483 SCV005667094 likely pathogenic Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23 2024-01-24 criteria provided, single submitter clinical testing

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