ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.802-9G>A

gnomAD frequency: 0.00003  dbSNP: rs761211705
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000383471 SCV000329777 pathogenic not provided 2023-07-27 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss-of-function (Krahn et al., 2007); In silico analysis supports a deleterious effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16141003, 19048948, 29797799, 25214167, 31589614, 33250842, 35169782, 17979987, 31069529)
Eurofins Ntd Llc (ga) RCV000383471 SCV000339477 pathogenic not provided 2017-01-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000400325 SCV000835887 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-01-07 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the CAPN3 gene. It does not directly change the encoded amino acid sequence of the CAPN3 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs761211705, gnomAD 0.006%). This variant has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 16141003, 17979987). 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: 280037). Studies have shown that this variant results in abnormal splicing and introduces a premature termination codon (PMID: 17979987). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV000383471 SCV001143421 pathogenic not provided 2019-06-21 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because it is below the disease allele frequency. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to negatively affect a known splice site. Occurs in three or more cases with a recessive pathogenic variant in the same gene.
Revvity Omics, Revvity RCV000383471 SCV002018085 pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002479996 SCV002784285 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 2022-05-25 criteria provided, single submitter clinical testing
Lifecell International Pvt. Ltd RCV000400325 SCV003853251 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A criteria provided, single submitter clinical testing A Homozygote Intron variant c.802-9G>A in Exon 5 of the CAPN3 gene that results in the amino acid substitution was identified. The observed variant has a minor allele frequency of 0.00002/0.00003 in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic [Variation ID: 280037]. The observed variant has been reported in individual(s) with limb-girdle muscular dystrophy. Studies have shown that this variant results in abnormal splicing and introduces a premature termination codon (Krahn M, et.al, 2007). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003475885 SCV004211518 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-02-10 criteria provided, single submitter clinical testing
Counsyl RCV000400325 SCV000791486 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-05-17 no assertion criteria provided clinical testing
Natera, Inc. RCV000400325 SCV001454327 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-09-16 no assertion criteria provided clinical testing

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