Submissions for variant NM_001009994.3(RIPPLY2):c.238A>T (p.Arg80Ter)

gnomAD frequency: 0.00024  dbSNP: rs201419367

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000275086	SCV000337717	uncertain significance	not provided	2015-12-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000275086	SCV002545437	pathogenic	not provided	2024-10-01	criteria provided, single submitter	clinical testing	RIPPLY2: PVS1:Strong, PM2, PM3, PP4, PS3:Supporting
Labcorp Genetics (formerly Invitae), Labcorp	RCV000275086	SCV003515263	uncertain significance	not provided	2023-10-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg80*) in the RIPPLY2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the RIPPLY2 protein. This variant is present in population databases (rs201419367, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with multiple segmentation defects (PMID: 25343988). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 221271). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV000207268	SCV003834817	pathogenic	Spondylocostal dysostosis 6, autosomal recessive	2022-12-05	criteria provided, single submitter	clinical testing
OMIM	RCV000207268	SCV000262593	pathogenic	Spondylocostal dysostosis 6, autosomal recessive	2015-03-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000275086	SCV001807180	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000275086	SCV001959299	pathogenic	not provided		no assertion criteria provided	clinical testing
GeneReviews	RCV002270021	SCV002555542	not provided	Spondylocostal dysostosis 2, autosomal recessive		no assertion provided	literature only