ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.280+2T>C

gnomAD frequency: 0.00001  dbSNP: rs770772281
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001377228 SCV001574503 likely pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2023-09-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the HSD17B4 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 HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454, 20673864). This variant is present in population databases (rs770772281, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1066269). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001581112 SCV001812065 likely pathogenic not provided 2019-08-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in an in-frame deletion of a critical region
Baylor Genetics RCV001826124 SCV004192423 pathogenic Bifunctional peroxisomal enzyme deficiency 2022-12-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001826124 SCV002075399 likely pathogenic Bifunctional peroxisomal enzyme deficiency 2020-02-06 no assertion criteria provided clinical testing

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