ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.4960-17C>A

gnomAD frequency: 0.00003  dbSNP: rs758048596
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513320 SCV000609229 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000513320 SCV000617983 uncertain significance not provided 2017-09-13 criteria provided, single submitter clinical testing The c.4960-17 C>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.4960-17 C>A variant is not observed in large population cohorts (Lek et al., 2016). Multiple in-silico splice prediction models predict that c.4960-17 C>A creates a cryptic splice acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.4960-17 C>A on splicing in this individual is unknown.
Labcorp Genetics (formerly Invitae), Labcorp RCV001857325 SCV002122466 likely pathogenic LAMA2-related muscular dystrophy 2024-01-11 criteria provided, single submitter clinical testing This sequence change falls in intron 34 of the LAMA2 gene. It does not directly change the encoded amino acid sequence of the LAMA2 protein. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has been observed in individuals with congenital muscular dystrophy (PMID: 32936536; Invitae). ClinVar contains an entry for this variant (Variation ID: 444699). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Baylor Genetics RCV003470642 SCV004190416 likely pathogenic Merosin deficient congenital muscular dystrophy 2024-02-18 criteria provided, single submitter clinical testing
Mendelics RCV003470642 SCV005373476 pathogenic Merosin deficient congenital muscular dystrophy 2024-10-07 criteria provided, single submitter clinical testing Observed in patient with Congenital Muscular Dystrophy. Likely causes splice disruption.
Department of Human Genetics, University Hospital Bern, Inselspital RCV003470642 SCV005619925 pathogenic Merosin deficient congenital muscular dystrophy 2024-07-01 criteria provided, single submitter research Pathogenic variants in the LAMA2 gene are associated with muscular dystrophy and follow an autosomal recessive inheritance pattern (OMIM 156225). Functional studies have demonstrated that the variant causes the retention of 15 base pairs of intron 34 in the mutant transcript, introducing a premature "TAG" stop codon and likely resulting in premature termination of translation (PMID: 39213089). This variant is listed in the gnomAD population database with an average frequency of approximately 0.001%. It has been observed in individuals diagnosed with congenital muscular dystrophy (PMID: 32936536, 39213089).
Fulgent Genetics, Fulgent Genetics RCV005044762 SCV005667095 likely pathogenic Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23 2024-05-17 criteria provided, single submitter clinical testing

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