ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.4717+1G>T (rs1131691660)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000494223 SCV000780870 likely pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing
Counsyl RCV000664588 SCV000788577 likely pathogenic Merosin deficient congenital muscular dystrophy 2017-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000494223 SCV000582586 pathogenic not provided 2015-09-23 criteria provided, single submitter clinical testing The c.4717+1G>T substitution in the LAMA2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 32. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.4717+1G>T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.4717+1G>T as a pathogenic variant.
Invitae RCV000654738 SCV000776637 likely pathogenic Laminin alpha 2-related dystrophy 2018-11-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 32 of the LAMA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LAMA2-related disease. ClinVar contains an entry for this variant (Variation ID: 429903). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894). 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.

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