ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.5260del (p.Lys1753_Val1754insTer)

gnomAD frequency: 0.00006  dbSNP: rs794727594
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000482229 SCV000229853 pathogenic not provided 2014-05-13 criteria provided, single submitter clinical testing
GeneDx RCV000482229 SCV000569375 pathogenic not provided 2024-08-27 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31127727, 25663498, 37476021, 35710456)
Labcorp Genetics (formerly Invitae), Labcorp RCV000533733 SCV000658709 pathogenic LAMA2-related muscular dystrophy 2023-07-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Val1754*) 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 (rs794727594, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with congenital muscular dystrophy (PMID: 25663498). ClinVar contains an entry for this variant (Variation ID: 196993).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000533733 SCV001362505 pathogenic LAMA2-related muscular dystrophy 2019-11-15 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.5260delG (p.Val1754X) 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 1.6e-05 in 249822 control chromosomes. c.5260delG has been reported in the literature in at-least one individual affected with Laminin alpha 2-related dystrophy (example, Lokken_2015). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a complete absence of Merosin protein staining by IHC and western blot analysis (Lokken_2015). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000482229 SCV001447452 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000177896 SCV004190428 pathogenic Merosin deficient congenital muscular dystrophy 2024-03-27 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000482229 SCV004811045 pathogenic not provided 2024-03-01 criteria provided, single submitter clinical testing LAMA2: PVS1, PM2, PM3
Counsyl RCV000177896 SCV000792345 likely pathogenic Merosin deficient congenital muscular dystrophy 2017-06-14 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000482229 SCV001807185 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000482229 SCV001953023 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000482229 SCV001971383 pathogenic not provided no assertion criteria provided clinical testing

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