ClinVar Miner

Submissions for variant NM_000426.3(LAMA2):c.1621A>G (p.Ser541Gly) (rs141363186)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000710155 SCV000110608 uncertain significance not provided 2015-04-17 criteria provided, single submitter clinical testing
GeneDx RCV000710155 SCV000329387 likely benign not provided 2021-01-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000078748 SCV000595512 uncertain significance not specified 2015-08-21 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710155 SCV000613961 likely benign not provided 2020-01-08 criteria provided, single submitter clinical testing
Invitae RCV001081996 SCV000658631 benign Laminin alpha 2-related dystrophy 2020-12-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001157936 SCV001319542 uncertain significance Congenital muscular dystrophy due to partial LAMA2 deficiency 2018-01-12 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000710155 SCV001713371 uncertain significance not provided 2021-02-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000710155 SCV001550736 likely benign not provided no assertion criteria provided clinical testing The LAMA2 p.Ser541Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs141363186) and ClinVar (classified as benign by Invitae, likely benign by GeneDx and a VUS by EGL Genetics, Genetics Services Laboratory (University of Chicago) and Athena Diagnostics). The variant was also identified in control databases in 465 of 282658 chromosomes (1 homozygous) at a frequency of 0.001645 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 357 of 129082 chromosomes (freq: 0.002766), Ashkenazi Jewish in 23 of 10368 chromosomes (freq: 0.002218), Other in 10 of 7222 chromosomes (freq: 0.001385), South Asian in 34 of 30616 chromosomes (freq: 0.001111), Latino in 31 of 35400 chromosomes (freq: 0.000876) and African in 10 of 24916 chromosomes (freq: 0.000401), while the variant was not observed in the East Asian and European (Finnish) populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Ser541 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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