ClinVar Miner

Submissions for variant NM_000102.4(CYP17A1):c.297+2T>C

gnomAD frequency: 0.00002  dbSNP: rs764723654
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498324 SCV000589610 pathogenic not provided 2017-06-16 criteria provided, single submitter clinical testing The c.297+2 T>C splice site variant has been previously reported in association with CYP17A1-associated disorders (Hwang et al., 2011; Dong et al., 2016). This variant destroys the canonical splice donor site in intron 1, and functional studies have shown c.297+2 T>C leads to abnormal splicing and a decrease in CYP17A1 protein expression (Hwang et al., 2011). The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be pathogenic.
Invitae RCV000498324 SCV001581377 pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the CYP17A1 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 CYP17A1 are known to be pathogenic (PMID: 10720067, 14747197, 17192295, 20197673, 24140098). This variant is present in population databases (rs764723654, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of CYP17A1-related disease (PMID: 21966534, 26980296). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS1+2T>C. ClinVar contains an entry for this variant (Variation ID: 431980). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 21966534). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000709945 SCV004215409 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2023-07-07 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000709945 SCV000840305 not provided Deficiency of steroid 17-alpha-monooxygenase no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc. RCV000709945 SCV001459687 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2020-09-16 no assertion criteria provided clinical testing

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