Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001014443 | SCV001175150 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-26 | criteria provided, single submitter | clinical testing | The c.210-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 4 in the PTEN gene. This nucleotide position is highly conserved in available vertebrate species.Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
Invitae | RCV001035561 | SCV001198890 | pathogenic | PTEN hamartoma tumor syndrome | 2019-02-21 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). Disruption of this splice site has been observed in individuals affected with Cowden syndrome (PMID: 28677221). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the PTEN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003396601 | SCV004103925 | likely pathogenic | PTEN-related condition | 2023-09-29 | criteria provided, single submitter | clinical testing | The PTEN c.210-2A>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is predicted to disrupt splicing by a machine learning in silico prediction algorithm (SpliceAI, Jaganathan K, et al. 2019. PubMed ID: 30661751), and aberrant splicing is likely to result in premature termination. Variants of this type in PTEN are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
Myriad Genetics, |
RCV003455084 | SCV004188765 | likely pathogenic | Cowden syndrome 1 | 2023-09-27 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |