ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.432+1G>A (rs1554395431)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624372 SCV000741973 pathogenic Inborn genetic diseases 2016-12-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000521677 SCV000618350 likely pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing The c.432+1 G>A likely pathogenic variant in the COL1A2 gene has not been reported as pathogenic or benign to our knowledge. This variant destroys the canonical splice donor site of intron nine and is predicted to cause skipping of exon nine, although it does not result in a shift in reading frame or a premature stop codon. Many other canonical splice site variants in the COL1A2 gene have been reported in HGMD (Stenson et al., 2014). Furthermore, c.432+1 G>A is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000689533 SCV000817187 pathogenic Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2017-11-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the COL1A2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with COL1A2-related disease (Invitae). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL1A2 are known to be pathogenic (PMID: 2993307, 3372533, 6092353, 16816023, 27510842). For these reasons, this variant has been classified as Pathogenic.

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