Submissions for variant NM_002890.3(RASA1):c.2698_2701del (p.Val900fs)

dbSNP: rs886041232

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000327372	SCV000329486	pathogenic	not provided	2015-12-21	criteria provided, single submitter	clinical testing	The c.2698_2701delGTTT pathogenic variant in the RASA1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2698_2701delGTTT variant causes a frameshift starting with codon Valine 900, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Val900PhefsX10. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2698_2701delGTTT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2698_2701delGTTT as a pathogenic variant.
Invitae	RCV001060687	SCV001225391	pathogenic	Capillary malformation-arteriovenous malformation syndrome	2023-02-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 279880). This premature translational stop signal has been observed in individual(s) with capillary malformation-arteriovenous malformation (PMID: 29891884). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val900Phefs*10) 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).