ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.396+1G>T

gnomAD frequency: 0.00001  dbSNP: rs770617208
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725186 SCV000334741 pathogenic not provided 2015-09-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000553357 SCV000658676 pathogenic LAMA2-related muscular dystrophy 2024-10-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 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). This variant is present in population databases (rs770617208, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with congenital muscular dystrophy (PMID: 30055037). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 282977). 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 RCV000725186 SCV002016460 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
GeneDx RCV000725186 SCV002584020 pathogenic not provided 2022-04-14 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18700894, 16199547, 32936536, 30055037)
3billion, Medical Genetics RCV003152703 SCV003841492 pathogenic Muscular dystrophy, limb-girdle, autosomal recessive 23 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000282977 / PMID: 30055037). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV000316746 SCV004190422 pathogenic Merosin deficient congenital muscular dystrophy 2023-10-14 criteria provided, single submitter clinical testing
Counsyl RCV000316746 SCV000795936 likely pathogenic Merosin deficient congenital muscular dystrophy 2017-11-30 no assertion criteria provided clinical testing

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