Submissions for variant NM_000426.3(LAMA2):c.6161A>G (p.Gln2054Arg) (rs56035053)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000178515	SCV000230610	uncertain significance	not provided	2015-02-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000192788	SCV000247812	uncertain significance	not specified	2015-04-05	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics	RCV000178515	SCV000280638	uncertain significance	not provided	2015-09-29	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
PreventionGenetics,PreventionGenetics	RCV000192788	SCV000304170	benign	not specified		criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000509541	SCV000611393	uncertain significance	Merosin deficient congenital muscular dystrophy	2017-05-23	criteria provided, single submitter	clinical testing
Invitae	RCV000549092	SCV000658733	uncertain significance	Laminin alpha 2-related dystrophy	2020-01-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine with arginine at codon 2054 of the LAMA2 protein (p.Gln2054Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs56035053, 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: 197478). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Athena Diagnostics Inc	RCV000178515	SCV000842624	uncertain significance	not provided	2017-11-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000178515	SCV000980463	likely benign	not provided	2018-05-22	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina	RCV001154910	SCV001316304	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.
GenomeConnect, ClinGen	RCV000509541	SCV000606884	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.