ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.5794+2T>A

gnomAD frequency: 0.00001  dbSNP: rs1266090046
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001593512 SCV001816550 pathogenic not provided 2023-07-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 28973083, 33146414)
Labcorp Genetics (formerly Invitae), Labcorp RCV005225442 SCV005863277 pathogenic Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2024-08-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 34 of the COL12A1 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 COL12A1 are known to be pathogenic (PMID: 24334604, 28973083). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive COL12A1-related conditions (PMID: 33146414). 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: 1215037). 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.

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