ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.2049_2050delAG (rs202247790)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genetic Medicine Research,Children's National Medical Center RCV000230453 SCV000265783 uncertain significance not specified 2015-12-01 criteria provided, single submitter research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078754 SCV000226026 pathogenic not provided 2013-11-08 criteria provided, single submitter clinical testing
GeneDx RCV000078754 SCV000583109 pathogenic not provided 2018-12-13 criteria provided, single submitter clinical testing The c.2049_2050delAG variant in the LAMA2 gene has been previously reported in individuals with merosin-deficient congenital muscular dystrophy who harbor an additional LAMA2 variant (Guicheney et al., 1998; Yang et al., 2015). The c.2049_2050delAG variant is observed in 5/24028 (0.0208%) alleles from individuals of African background and 34/277008 total alleles in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). The c.2049_2050delAG variant causes a frameshift starting with codon Arginine 683, changes this amino acid to a Serine residue and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Arg683SerfsX21. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret c.2049_2050delAG as a pathogenic variant.
GeneReviews RCV000031899 SCV000054523 pathologic Merosin deficient congenital muscular dystrophy 2012-06-07 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000557045 SCV000658642 pathogenic Laminin alpha 2-related dystrophy 2018-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg683Serfs*21) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs751627052, ExAC 0.01%). This variant has been reported in the literature in multiple individuals affected with congenital muscular dystrophy (PMID: 9541105, 25544356, 18700894, 24611677). This variant is also known in the literature as 2098delAG and p.Lys682Lysfs*22. ClinVar contains entries for this variant (Variation ID: 38340, 216956). Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894). For these reasons, this variant has been classified as Pathogenic.

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