Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002232788 | SCV000762153 | pathogenic | Capillary malformation-arteriovenous malformation syndrome | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 19 of the RASA1 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 RASA1 are known to be pathogenic (PMID: 24038909). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with capillary malformation-arteriovenous malformation (CM-AVM) (PMID: 18446851, 23164092). ClinVar contains an entry for this variant (Variation ID: 533449). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000680836 | SCV000808285 | pathogenic | not provided | 2018-03-29 | criteria provided, single submitter | clinical testing | The c.2603+1 G>A variant in the RASA1 gene has been reported in several patients with features of CM-AVM syndrome (Revencu et al., 2012; Behr et al., 2012). This variant destroys the canonical splice donor site in intron 19 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either 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. Other splice site variants in the RASA1 gene have been reported in HGMD in association with RASA1-related disorders (Stenson et al., 2014). Furthermore, the c.2603+1 G>A variant is not observed in large population cohorts (Lek et al., 2016). |
Institute of Medical Genetics and Applied Genomics, |
RCV002307569 | SCV002604924 | pathogenic | Capillary malformation-arteriovenous malformation 1 | 2022-11-18 | criteria provided, single submitter | clinical testing | |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV002307569 | SCV004174079 | pathogenic | Capillary malformation-arteriovenous malformation 1 | no assertion criteria provided | clinical testing |