ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.2115+1G>A

gnomAD frequency: 0.00001  dbSNP: rs766917640
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671447 SCV000796423 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-12-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000671447 SCV001226649 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-06-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 of the CAPN3 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 CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is present in population databases (rs766917640, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 555599). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004586865 SCV005076871 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2024-04-09 criteria provided, single submitter clinical testing Variant summary: CAPN3 c.2115+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251208 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2115+1G>A in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 555599). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Natera, Inc. RCV000671447 SCV002085553 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2021-08-21 no assertion criteria provided clinical testing
Baylor Genetics RCV003472137 SCV004211528 likely pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2023-10-18 flagged submission clinical testing

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