ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.2185-2A>G

gnomAD frequency: 0.00001  dbSNP: rs886041335
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000343664 SCV000329779 pathogenic not provided 2018-08-29 criteria provided, single submitter clinical testing The c.2185-2 A>G splice site variant in the CAPN3 gene has been previously reported in association with limb-girdle muscular dystrophy (Richard et al., 1999; CAPN3 LOVD). This pathogenic variant destroys the canonical splice acceptor site in intron 20, and is expected to cause abnormal gene splicing. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, c.2185-2 A>G is considered a pathogenic variant.
Athena Diagnostics Inc RCV000343664 SCV000612639 pathogenic not provided 2016-12-30 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000343664 SCV000701845 pathogenic not provided 2016-10-17 criteria provided, single submitter clinical testing
Counsyl RCV000593825 SCV000799807 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-05-08 criteria provided, single submitter clinical testing
Invitae RCV000593825 SCV002968421 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2023-09-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 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 not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of autosomal recessive limb-girdle muscular dystrophy (PMID: 10330340, 31069529; Invitae). ClinVar contains an entry for this variant (Variation ID: 280039). 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.
Baylor Genetics RCV003463736 SCV004213755 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2023-07-06 criteria provided, single submitter clinical testing

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