Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | |
Genome |
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, |
RCV000709945 | SCV001459687 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2020-09-16 | no assertion criteria provided | clinical testing |