ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.6128A>G (p.Gln2043Arg) (rs144155507)

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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 Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224036 SCV000280813 uncertain significance not provided 2015-12-23 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000341200 SCV000460056 uncertain significance Congenital muscular dystrophy due to partial LAMA2 deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000522850 SCV000618096 uncertain significance not specified 2017-06-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LAMA2 gene. The Q2043R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q2043R variant is observed in 73/66,630 (0.1%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q2043R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000535681 SCV000658729 uncertain significance Laminin alpha 2-related dystrophy 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 2043 of the LAMA2 protein (p.Gln2043Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs144155507, ExAC 0.1%). This variant has not been reported in the literature in individuals with LAMA2-related disease. ClinVar contains an entry for this variant (Variation ID: 235327). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000522850 SCV000804876 uncertain significance not specified 2017-06-20 no assertion criteria provided clinical testing

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