ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.8836G>A (p.Gly2946Arg)

gnomAD frequency: 0.00006  dbSNP: rs370843758
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000294689 SCV000460092 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.
Counsyl RCV000673324 SCV000798512 uncertain significance Merosin deficient congenital muscular dystrophy 2018-03-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000691737 SCV000819527 likely benign LAMA2-related muscular dystrophy 2023-12-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002229896 SCV002511500 uncertain significance not specified 2022-04-08 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.8836G>A (p.Gly2946Arg) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) 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 0.00012 in 251352 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in LAMA2 causing Laminin Alpha 2-Related Dystrophy (0.00012 vs 0.0022), allowing no conclusion about variant significance. c.8836G>A has been reported in the literature in at least one compound heterozygous individual affected with Laminin Alpha 2-Related Dystrophy (Sframeli_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all three classified the variant as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002487559 SCV002780092 uncertain significance Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23 2021-10-08 criteria provided, single submitter clinical testing

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