ClinVar Miner

Submissions for variant NM_002890.3(RASA1):c.2125C>T (p.Arg709Ter)

dbSNP: rs1554049422
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521374 SCV000617840 pathogenic not provided 2017-09-22 criteria provided, single submitter clinical testing The R709X variant in the RASA1 gene has been reported in at least four unrelated individuals with CV-AVM, three of whom had affected family members who also harbored the R709X variant (Revencu et al., 2008; Revencu et al., 2016; Grillner et al., 2016). R709X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the RASA1 gene have been reported in Human Gene Mutation Database in association with CV-AVM (Stenson et al., 2014). Furthermore, the R709X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV001386102 SCV001586205 pathogenic Capillary malformation-arteriovenous malformation syndrome 2022-08-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 449560). This premature translational stop signal has been observed in individuals with capillary malformation-arteriovenous malformations (CM-AVM) (PMID: 18446851, 24038909, 26499346, 29024832). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg709*) in the RASA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RASA1 are known to be pathogenic (PMID: 24038909).

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