ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.2462C>T (p.Thr821Met)

gnomAD frequency: 0.00217  dbSNP: rs117422805
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000723613 SCV000196850 likely benign not provided 2020-04-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24611677, 24082139, 27896284, 23891399)
Eurofins NTD LLC (GA) RCV000723613 SCV000331387 uncertain significance not provided 2015-06-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000149994 SCV000595502 uncertain significance not specified 2016-09-24 criteria provided, single submitter clinical testing
Invitae RCV001084610 SCV000658653 benign LAMA2-related muscular dystrophy 2021-12-18 criteria provided, single submitter clinical testing
Counsyl RCV000670870 SCV000795783 uncertain significance Merosin deficient congenital muscular dystrophy 2017-11-25 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001156369 SCV001317862 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.
CeGaT Center for Human Genetics Tuebingen RCV000723613 SCV001500925 uncertain significance not provided 2020-07-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000149994 SCV002556232 likely benign not specified 2022-06-29 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.2462C>T (p.Thr821Met) 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 0.002 in 282674 control chromosomes, predominantly at a frequency of 0.0036 within the Finnish subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Finnish control individuals in the gnomAD database is approximately two 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 a benign polymorphism found primarily in populations of Finnish origin. c.2462C>T has been reported in the literature in at least two homozygous individuals affected with Laminin Alpha 2-Related Dystrophy (example Xiong_2015, Ge_2019, Tan_2021). However, these reports do not provide unequivocal evidence for an association of the variant with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight clinical-significance assessments for this variant have been submitted to ClinVar after 2014 with conflicting assessments (VUS n=5, likely benign n=2, benign n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252050 SCV001427798 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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