ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2926+1G>A (rs267608179)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169032 SCV000220182 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2014-03-22 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000599041 SCV000340724 pathogenic not provided 2016-03-25 criteria provided, single submitter clinical testing
GeneDx RCV000599041 SCV000709922 likely pathogenic not provided 2018-01-19 criteria provided, single submitter clinical testing The c.2926+1G>A variant in the PEX1 gene has been reported previously in association with Zellweger spectrum disorder (Reuber et al., 1997; Yik et al., 2009). This splice site variant destroys the canonical splice donor site in intron 18. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2926+1G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.2926+1G>A as a likely pathogenic variant.
Invitae RCV000169032 SCV000963840 pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2018-12-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the PEX1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs267608179, ExAC 0.004%). This variant has been observed in several individuals affected with Zellweger syndrome spectrum disorders (PMID: 19105186, 15542397, 21031596). ClinVar contains an entry for this variant (Variation ID: 188729). This variant has been reported to affect PEX1 protein function (PMID: 9398847). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). For these reasons, this variant has been classified as Pathogenic.

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