ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.112+1G>A

gnomAD frequency: 0.00001  dbSNP: rs398123367
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790741 SCV000224218 pathogenic not provided 2014-11-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001064438 SCV001229341 pathogenic LAMA2-related muscular dystrophy 2024-03-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the LAMA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with merosin deficient congenital muscular dystrophy (PMID: 20207543). ClinVar contains an entry for this variant (Variation ID: 92937). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000790741 SCV002016434 pathogenic not provided 2020-08-21 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001810421 SCV002060273 likely pathogenic Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23 2021-11-16 criteria provided, single submitter clinical testing NM_000426.3(LAMA2):c.112+1G>A is a canonical splice variant classified as likely pathogenic in the context of muscular dystrophy, LAMA2-related. c.112+1G>A has been observed in cases with relevant disease (PMID: 20207543). Functional assessments of this variant are not available in the literature. c.112+1G>A has been observed in population frequency databases (gnomAD: NFE 0.005%). In summary, NM_000426.3(LAMA2):c.112+1G>A is a canonical splice variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening.
Athena Diagnostics RCV000790741 SCV002771705 pathogenic not provided 2022-04-05 criteria provided, single submitter clinical testing This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with merosin-deficient congenital muscular dystrophy.
Baylor Genetics RCV003466973 SCV004190470 pathogenic Merosin deficient congenital muscular dystrophy 2023-11-25 criteria provided, single submitter clinical testing

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