ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.4487C>T (p.Ala1496Val)

gnomAD frequency: 0.00338  dbSNP: rs147077184
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000659062 SCV000229395 uncertain significance not provided 2016-06-09 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000194655 SCV000247808 uncertain significance not specified 2014-12-01 criteria provided, single submitter clinical testing
Center for Genetic Medicine Research,Children's National Medical Center RCV000194655 SCV000265802 uncertain significance not specified 2015-12-01 criteria provided, single submitter research
GeneDx RCV000659062 SCV000518856 benign not provided 2018-04-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24957499, 28133863, 27854218)
Invitae RCV001081183 SCV000658688 benign LAMA2-related muscular dystrophy 2021-12-18 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000659062 SCV000780869 uncertain significance not provided 2018-02-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories,Mayo Clinic RCV000509423 SCV000782654 uncertain significance Merosin deficient congenital muscular dystrophy 2017-06-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000659062 SCV000842619 benign not provided 2017-12-15 criteria provided, single submitter clinical testing
Mendelics RCV000509423 SCV001137222 uncertain significance Merosin deficient congenital muscular dystrophy 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001152676 SCV001313901 uncertain significance Congenital muscular dystrophy due to partial LAMA2 deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000194655 SCV002103481 likely benign not specified 2022-02-23 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.4487C>T (p.Ala1496Val) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0037 in 251380 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 1.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMA2 causing Laminin Alpha 2-Related Dystrophy phenotype (0.0022), strongly suggesting that the variant is benign. Although reported in mutational updates (example, Oliviera_2018), to our knowledge, no penetrant association of c.4487C>T in individuals affected with Laminin Alpha 2-Related Dystrophy and no supporting experimental evidence demonstrating its impact on protein function have been reported. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
GenomeConnect, ClinGen RCV000509423 SCV000607097 not provided Merosin deficient congenital muscular dystrophy no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
OMIM RCV000709620 SCV000839536 pathogenic Muscular dystrophy, limb-girdle, autosomal recessive 23 2018-10-05 no assertion criteria provided literature only
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000659062 SCV001798374 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000659062 SCV001951366 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000194655 SCV001964121 benign not specified no assertion criteria provided clinical testing

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